Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescen...Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.展开更多
Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate si...Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.展开更多
In recent years,the emergence of nanotechnology experienced incredible development in the field of medical sciences.During the past decade,investigating the characteristics of nanoparticles during fluid flow has been ...In recent years,the emergence of nanotechnology experienced incredible development in the field of medical sciences.During the past decade,investigating the characteristics of nanoparticles during fluid flow has been one of the intriguing issues.Nanoparticle distribution and uniformity have emerged as substantial criteria in both medical and engineering applications.Adverse effects of chemotherapy on healthy tissues are known to be a significant concern during cancer therapy.A novel treatment method of magnetic drug targeting(MDT)has emerged as a promising topical cancer treatment along with some attractive advantages of improving efficacy,fewer side effects,and reduce drug dose.During magnetic drug targeting,the appropriate movement of nanoparticles(magnetic)as carriers is essential for the therapeutic process in the blood clot removal,infection treatment,and tumor cell treatment.In this study,we have numerically investigated the behavior of an unsteady blood flowinfused with magnetic nanoparticles during MDT under the influence of a uniform external magnetic field in a microtube.An optimal homotopy asymptotic method(OHAM)is employed to compute the governing equation for unsteady electromagnetohydrodynamics flow.The influence of Hartmann number(Ha),particle mass parameter(G),particle concentration parameter(R),and electro-osmotic parameter(k)is investigated on the velocity of magnetic nanoparticles and blood flow.Results obtained show that the electro-osmotic parameter,along with Hartmann’s number,dramatically affects the velocity of magnetic nanoparticles,blood flow velocity,and flow rate.Moreover,results also reveal that at a higher Hartman number,homogeneity in nanoparticles distribution improved considerably.The particle concentration andmass parameters effectively influence the capturing effect on nanoparticles in the blood flow using a micro-tube for magnetic drug targeting.Lastly,investigation also indicates that the OHAM analysis is efficient and quick to handle the system of nonlinear equations.展开更多
The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,w...The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,we first prepared the DTX-loaded activated carbon nanoparticles(DTX-AC-NPs)by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon.We then prepared DTX-loaded nanoliposomes(DTX-LPs)by the proliposome method.The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro.The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites.The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies.DTX-AC-NPs significantly increased DTX-AUC_((0-24)) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo.This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.展开更多
Objective:Human pancreatic cancer is one of the most common clinical malignancies.The effect of comprehensive treatment based on surgery is general.The effects of chemotherapy were not obvious mainly because of lack o...Objective:Human pancreatic cancer is one of the most common clinical malignancies.The effect of comprehensive treatment based on surgery is general.The effects of chemotherapy were not obvious mainly because of lack of targeting and chemoresistance in pancreatic cancer.This study aimed to investigate the effects of folate receptor(FR)-mediated gemcitabine FA-Chi-Gem nanoparticles with a core-shell structure by electrostatic spray on pancreatic cancer.Methods:In this study,the levels of expression of FR in six human pancreatic cancer cell lines were studied by immunohistochemical analysis.The uptake rate of isothiocyanate-labeled FA-Chi nanoparticles in FR high expression cell line COLO357 was assessed by fluorescence microscope and the inhibition rate of FAChi-Gem nanoparticles on COLO357 cells was evaluated by MTT assay.Moreover,the biodistribution of PEG-FA-ICGDER02-Chi in the orthotopic pancreatic tumor model was observed using near-infrared imaging and the human pancreatic cancer orthotopic xenografts were treated with different nanoparticles and normal saline control.Results:The expression of FR in COLO357 was the highest among the six pancreatic cancer cell lines.The FR mainly distributed on cell membrane and fewer in the cytoplasm in pancreatic cancer.Moreover,the absorption rate of the FA-Chi-Gem nanoparticles was more than the Chi nanoparticles without FA modified.The proliferation of COLO357 was significantly inhibited by FA-Chi-Gem nanoparticles.The PEG-FAICGDER02-Chi nanoparticles were enriched in tumor tissue in human pancreatic cancer xenografts,while non-targeted nanoparticles were mainly in normal liver tissue.PEG-FA-Gem-Chi significantly inhibited the growth of human pancreatic cancer xenografts(PEG-FA-Gem-Chi vs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-Chi nanoparticles might be an effective targeted drug for treating human FR-positive pancreatic cancer.展开更多
Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugate...Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.展开更多
In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular en...In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.展开更多
Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium(RPE) transplantation represents a promising therapy....Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium(RPE) transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1(MCP-1) expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor(VEGF) is upregulated by MCP-1mediated inflammation and results in the formation of choroidal neovascularization(CNV). We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles(SPIONs). Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging(MRI). This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.展开更多
The aim of this paper was to evaluate controlled release behavior and the therapeutic efficacy of 5-FU-loaded Poly(lactic acid) (PLA)microspheres to human gastric cancer xenograft, and the targeting effect of VEGF/5-F...The aim of this paper was to evaluate controlled release behavior and the therapeutic efficacy of 5-FU-loaded Poly(lactic acid) (PLA)microspheres to human gastric cancer xenograft, and the targeting effect of VEGF/5-FU loaded PLA nanoparticles. 5-FU-loaded PLA microspheres were prepared by an emulsion evaporation method, and were characterized by scanning electron microscopy (SEM). 5-FU loaded PLA nanoparticles were characterized by (TEM), and particle size analyzer determined the distribution of nanoparticles size. The release performances of 5-FU microspheres in vitro were studied in PH 7.4 phosphate buffered saline. The therapeutic efficacy of 5-FU-loaded PLA microspheres in vivo were studied using MGC-803 (human stomach cancer) xenograft. 32 nude mice were divided into four groups (n =8), 5-FU loaded PLA microspheres were injected at tumor site. VEGF121 monoclonal antibody was connected with 5-FU loaded PLA nanoparticles through carbodimide. The targeted effect of VEGF 5-FU loaded nanoparticles in vivo were observed by single photon emission computed tomography (SPECT) after tail vein injection at 1 h and 2 h. SEM observation showed that microspheres were spherical, and the diameters of two kinds of microspheres were 1 μm and 5 μm respectively. The mean diameter of nanoparticles was 191.0 nm, and the index of polydispersity was 0.202. The drug was released following biphasic kinetics, initial burst and the following steady phase. 1 μm and 5 μm 5-FU-loaded microspheres both resulted in increased life span (1 μm microspheres median survival time=40.63 days, 5 μm microspheres median survival time=62.25 days), against 5-FU pure drug (median survival time=14.5 days). These results strongly suggest that 5-FU-loaded PLA microspheres increase life span of nude mice bearing MGC-803 tumors. After injection for 2 h, almost all the VEGF/5-FU loaded PLA nanoparticles could centralize at the human gastric cancer xenograft sites. That demonstrated VEGF monoclonal antibody remain its bioactivity after connection with nanoparticles, VEGF/5-FU loaded PLA nanoparticles had very exact targeting function for gastric tumor xenograft.展开更多
Particle shape has been recognized as one of the key properties of nanoparticles in biomedical applications including targeted drug delivery.Targeting ability of shape-engineered particles depends largely on targeting...Particle shape has been recognized as one of the key properties of nanoparticles in biomedical applications including targeted drug delivery.Targeting ability of shape-engineered particles depends largely on targeting ligands conjugated on the particle surface.However,poor capacity for surface ligand conjugation remains a problem in anisotropic nanoparticles made with biodegradable polymers such as PLGA.In this study,we prepared anisotropic PLGA nanoparticles with abundant conjugatable surface functional groups by a film stretching-based fabrication method with poly(ethylene-alt-maleic acid)(PEMA).Scanning electron microscopy images showed that microrods and nanorods were successfully fabricated by the PEMA-based film stretching method.The presence of surface carboxylic acid groups was confirmed by confocal microscopy and zeta potential measurements.Using the improved film-stretching method,the amount of protein conjugated to the surface of nanorods was increased three-fold.Transferrin-conjugated,nanorods fabricated by the improved method exhibited higher binding and internalization than unmodified counterparts.Therefore,the PEMA-based film-stretching system presented in this study would be a promising fabrication method for non-spherical biodegradable polymeric micro-and nanoparticles with high capacity of surface modifications for enhanced targeted delivery.展开更多
Venous and arterial thrombosis are closely related to many severe diseases, especially to cardiovascular and cerebrovasular disorders. Thrombolytic therapy has been proven to be an effective method to treat such disea...Venous and arterial thrombosis are closely related to many severe diseases, especially to cardiovascular and cerebrovasular disorders. Thrombolytic therapy has been proven to be an effective method to treat such disease, which decreased the mortality and morbidity greatly.展开更多
The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tu...The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.展开更多
About 30% of human breast cancers are human epidermal growth factor receptor 2(HER2)+. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of do...About 30% of human breast cancers are human epidermal growth factor receptor 2(HER2)+. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2+cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clinical outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the development of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional compartimentalization, which allows to combine the specific target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photothermal ablation or in photodynamic therapy have been functionalized in order to match specificity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2+breast cancer and anti-HER2 therapy, in particular deepening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted na-noparticles for HER2+ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical practice; however promising results encourage an upcoming translation of this research for the next future.展开更多
Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile attributes.Concurrently,magnetically actuated micro/na...Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile attributes.Concurrently,magnetically actuated micro/nano-robots(MNRs)offer distinct advantages,such as untethered and precise manipulation.The fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug delivery.Here,we report a MOF-based magnetic microrobot swarm(MMRS)for targeted therapy.Our approach overcomes limitations associated with a single MNR,including limited drug loading and the risk of loss during manipulation.We select Zeolitic Imidazolate Framework-8(ZIF-8)as the drug vehicle for its superior loading potential and p H-sensitive decomposition.Our design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8,enabling collective behaviors under actuation.Tuning the yaw angle of alternating magnetic fields and nanoparticles'amount,the MMRSs with controllable size achieve instantaneous transformation among different configurations,including vortex-like swarms,chain-like swarms,and elliptical swarms,facilitating adaptation to environmental variations.Transported to the subcutaneous T24 tumor site,the MMRSs with encapsulated doxorubicin(DOX)automatically degrade and release the drug,leading to a dramatic reduction of the tumor in vivo.Our investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms,ushering in new avenues for accurate and non-invasive targeted drug delivery.展开更多
Edible plant derived exosome-like nanoparticles(ELNs)have been shown to have multiple nutraceutical functions.However,the diversity of plant materials makes the plant derived ELN study challenging.More efforts are sti...Edible plant derived exosome-like nanoparticles(ELNs)have been shown to have multiple nutraceutical functions.However,the diversity of plant materials makes the plant derived ELN study challenging.More efforts are still needed to explore the feasible isolation methods of edible plant derived ELNs and the possible roles of food-derived ELNs in improving human health.In this study,a size exclusion chromatography based method was compared with the traditional ultracentrifugation method to isolate blueberry derived ELNs(B-ELNs),and the miRNA profile of B-ELNs was analyzed by high-throughput sequencing.A total of 36 miRNAs were found to be enriched in B-ELNs compared with berry tissue,and their potential cross-kingdom human gene targets were further predicted.Results showed that size exclusion chromatography was effective for B-ELN isolation.The most abundant miRNAs in B-ELNs mainly belonged to the miR166 family and miR396 family.Target gene prediction indicated that B-ELNs could potentially regulate pathways related to the human digestive system,immune system and infectious diseases.展开更多
Radiotherapy,where ionizing radiation is locally delivered either through an external beam or by surgically implanting radionuclide-based seeds in the tumor,is one of the gold standard treatments for cancer.Due to the...Radiotherapy,where ionizing radiation is locally delivered either through an external beam or by surgically implanting radionuclide-based seeds in the tumor,is one of the gold standard treatments for cancer.Due to the non-selective nature of radiation,healthy tissue surrounding the cancerous region is usually affected by the treatment.Hence,new strategies,including targeted alpha therapy,are being studied to improve the selectivity of the treatment and minimize side effects.Several challenges,however,limit the current development of targeted radiotherapy,such as the functionalization of the therapeutic agent with targeting vectors and controlling the release of recoiling daughters.Nanoparticles offer unique opportunities as drug delivery vehicles,since they are biocompatible,enhance the cellular uptake of drugs,and are easily functionalized with targeting molecules.In this review,we examine how nanoparticles can be used for targeted radiotherapy,either as sensitizers of external beams or as delivery vehicles for therapeutic radionuclides.We describe the clinical relevance of different types of nanoparticles,followed by an analysis of how these nanoconstructs can solve some of the main limitations of conventional radiotherapy.Finally,we critically discuss the current situation of nanoparticle-based radiotherapy in clinical settings and challenges that need to be overcome in the future for further development of the field.展开更多
Glioblastoma(GBM),the deadliest form of brain cancer,presents long-standing problems due to its localization.Chimeric antigen receptor(CAR)T cell immunotherapy has emerged as a powerful strategy to treat cancer.IL-13-...Glioblastoma(GBM),the deadliest form of brain cancer,presents long-standing problems due to its localization.Chimeric antigen receptor(CAR)T cell immunotherapy has emerged as a powerful strategy to treat cancer.IL-13-receptor-α2(IL13Rα2),present in over 75%of GBMs,has been recognized as an attractive candidate for antiglioblastoma therapy.Here,we propose a novel multidisciplinary approach to target brain tumors using a combination of fluorescent,therapeutic nanoparticles and CAR T cells modified with a targeted-quadruplemutant of IL13(TQM-13)shown to have high binding affinity to IL13Rα2-expressing glioblastoma cells with low off-target toxicity.Azide-alkyne cycloaddition conjugation of nanoparticles to the surface of T cells allowed a facile,selective,and high-yielding clicking of the nanoparticles.Nanoparticles clicked onto T cells were retained for at least 8 days showing that the linkage is stable and promising a suitable time window for in vivo delivery.T cells clicked with doxorubicin-loaded nanoparticles showed a higher cytotoxic effect in vitro compared to bare T cells.In vitro and in vivo T cells expressing TQM-13 served as delivery shuttles for nanoparticles and significantly increased the number of nanoparticles reaching brain tumors compared to nanoparticles alone.This work represents a new platform to allow the delivery of therapeutic nanoparticles and T cells to solid tumors.展开更多
The development of nanomedicines provides new opportunities for the treatment of atherosclerosis(AS)due to their great advantages such as the improved drug solubility,enhanced bioavailability and reduced side effects....The development of nanomedicines provides new opportunities for the treatment of atherosclerosis(AS)due to their great advantages such as the improved drug solubility,enhanced bioavailability and reduced side effects.Despite these advantages,nanomedicines are still facing some challenges.The problems remain in the short circulation life,lack of specific targeting and poor drug release controllability.In order to overcome the shortages of conventional nanomedicines,the combination of biomimetic strategy with smart nanoagents has been proposed.In light with the high reactive oxygen species(ROS)level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS,we fabricated ROS-responsive biomimetic nanoparticles(NPs),which camouflaged macrophage membrane(MM)on ROS-responsive NPs loaded with rapamycin(RNPs)for potential application in AS therapy.The resulting ROSresponsive biomimetic NPs(MM/RNPs)exhibited favorable hydrodynamic size with negative surface charge,retained the functional proteins from MM,and showed ROS-responsive drug release.Because of the biomimetic camouflaging on surface,MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells.Meanwhile,MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro.Furthermore,the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation.Consequently,these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.展开更多
Superparamagnetic iron oxide(SPIO)nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility.A variety of studies have shown the e...Superparamagnetic iron oxide(SPIO)nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility.A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles,such as surface-coated,targeted ligandconjugated,and/or drug-loaded SPIO nanoparticles,as powerful tools for targeted imaging and therapy.Moreover,the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment.In the present review,we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis,targeted therapy,and cancer imaging.展开更多
基金supported by Dalian Youth Science and Technology Star Project(2020RQ121)the National Science Fund for Distinguished Young Scholars of China(31925031)+1 种基金Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-211)Liaoning Province Education Administration(J2020101)。
文摘Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.
基金supported by the Deputy Research and Technology, Ardabil University of Medical Sciences。
文摘Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.
基金the research grant of Jeju National University in 2020,the Basic Science Research Program through the National Research Foundation of Korea(NRF)grant funded by the Korea Government(Ministry of Science and ICT)(NRF-2018R1A4A1025998)Higher Education Commission of Pakistan(Project No.210-3800/NRPU/R&D/HEC/1530).
文摘In recent years,the emergence of nanotechnology experienced incredible development in the field of medical sciences.During the past decade,investigating the characteristics of nanoparticles during fluid flow has been one of the intriguing issues.Nanoparticle distribution and uniformity have emerged as substantial criteria in both medical and engineering applications.Adverse effects of chemotherapy on healthy tissues are known to be a significant concern during cancer therapy.A novel treatment method of magnetic drug targeting(MDT)has emerged as a promising topical cancer treatment along with some attractive advantages of improving efficacy,fewer side effects,and reduce drug dose.During magnetic drug targeting,the appropriate movement of nanoparticles(magnetic)as carriers is essential for the therapeutic process in the blood clot removal,infection treatment,and tumor cell treatment.In this study,we have numerically investigated the behavior of an unsteady blood flowinfused with magnetic nanoparticles during MDT under the influence of a uniform external magnetic field in a microtube.An optimal homotopy asymptotic method(OHAM)is employed to compute the governing equation for unsteady electromagnetohydrodynamics flow.The influence of Hartmann number(Ha),particle mass parameter(G),particle concentration parameter(R),and electro-osmotic parameter(k)is investigated on the velocity of magnetic nanoparticles and blood flow.Results obtained show that the electro-osmotic parameter,along with Hartmann’s number,dramatically affects the velocity of magnetic nanoparticles,blood flow velocity,and flow rate.Moreover,results also reveal that at a higher Hartman number,homogeneity in nanoparticles distribution improved considerably.The particle concentration andmass parameters effectively influence the capturing effect on nanoparticles in the blood flow using a micro-tube for magnetic drug targeting.Lastly,investigation also indicates that the OHAM analysis is efficient and quick to handle the system of nonlinear equations.
基金the support of Pharmacy Laboratory Centre and Animal Centre of Shenyang Pharmaceutical Universitysupported by the State Key Laboratory(Long-acting and Targeting Drug Delivery System)the Special Construction Project(Taishan ScholarePharmacy Specially Recruited Experts).
文摘The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,we first prepared the DTX-loaded activated carbon nanoparticles(DTX-AC-NPs)by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon.We then prepared DTX-loaded nanoliposomes(DTX-LPs)by the proliposome method.The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro.The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites.The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies.DTX-AC-NPs significantly increased DTX-AUC_((0-24)) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo.This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.
基金supported by the National Natural Science Foundation of China(No.81071967 and 30872500)the Natural Science Foundation of Jiangsu province(Project No:BK2010242)
文摘Objective:Human pancreatic cancer is one of the most common clinical malignancies.The effect of comprehensive treatment based on surgery is general.The effects of chemotherapy were not obvious mainly because of lack of targeting and chemoresistance in pancreatic cancer.This study aimed to investigate the effects of folate receptor(FR)-mediated gemcitabine FA-Chi-Gem nanoparticles with a core-shell structure by electrostatic spray on pancreatic cancer.Methods:In this study,the levels of expression of FR in six human pancreatic cancer cell lines were studied by immunohistochemical analysis.The uptake rate of isothiocyanate-labeled FA-Chi nanoparticles in FR high expression cell line COLO357 was assessed by fluorescence microscope and the inhibition rate of FAChi-Gem nanoparticles on COLO357 cells was evaluated by MTT assay.Moreover,the biodistribution of PEG-FA-ICGDER02-Chi in the orthotopic pancreatic tumor model was observed using near-infrared imaging and the human pancreatic cancer orthotopic xenografts were treated with different nanoparticles and normal saline control.Results:The expression of FR in COLO357 was the highest among the six pancreatic cancer cell lines.The FR mainly distributed on cell membrane and fewer in the cytoplasm in pancreatic cancer.Moreover,the absorption rate of the FA-Chi-Gem nanoparticles was more than the Chi nanoparticles without FA modified.The proliferation of COLO357 was significantly inhibited by FA-Chi-Gem nanoparticles.The PEG-FAICGDER02-Chi nanoparticles were enriched in tumor tissue in human pancreatic cancer xenografts,while non-targeted nanoparticles were mainly in normal liver tissue.PEG-FA-Gem-Chi significantly inhibited the growth of human pancreatic cancer xenografts(PEG-FA-Gem-Chi vs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-Chi nanoparticles might be an effective targeted drug for treating human FR-positive pancreatic cancer.
基金Projects(31201074,81371013) supported by the National Natural Science Foundation of ChinaProject(2011105102016) supported by the Key Program of Medical Health of Dongguan City,Guangdong Province,ChinaProject(2011108102026) supported by Dongguan Universities Program,China
文摘Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.
文摘In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.
基金Supported by the National Natural Science Foundation of China(No.81100670)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry of China
文摘Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium(RPE) transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1(MCP-1) expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor(VEGF) is upregulated by MCP-1mediated inflammation and results in the formation of choroidal neovascularization(CNV). We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles(SPIONs). Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging(MRI). This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.
文摘The aim of this paper was to evaluate controlled release behavior and the therapeutic efficacy of 5-FU-loaded Poly(lactic acid) (PLA)microspheres to human gastric cancer xenograft, and the targeting effect of VEGF/5-FU loaded PLA nanoparticles. 5-FU-loaded PLA microspheres were prepared by an emulsion evaporation method, and were characterized by scanning electron microscopy (SEM). 5-FU loaded PLA nanoparticles were characterized by (TEM), and particle size analyzer determined the distribution of nanoparticles size. The release performances of 5-FU microspheres in vitro were studied in PH 7.4 phosphate buffered saline. The therapeutic efficacy of 5-FU-loaded PLA microspheres in vivo were studied using MGC-803 (human stomach cancer) xenograft. 32 nude mice were divided into four groups (n =8), 5-FU loaded PLA microspheres were injected at tumor site. VEGF121 monoclonal antibody was connected with 5-FU loaded PLA nanoparticles through carbodimide. The targeted effect of VEGF 5-FU loaded nanoparticles in vivo were observed by single photon emission computed tomography (SPECT) after tail vein injection at 1 h and 2 h. SEM observation showed that microspheres were spherical, and the diameters of two kinds of microspheres were 1 μm and 5 μm respectively. The mean diameter of nanoparticles was 191.0 nm, and the index of polydispersity was 0.202. The drug was released following biphasic kinetics, initial burst and the following steady phase. 1 μm and 5 μm 5-FU-loaded microspheres both resulted in increased life span (1 μm microspheres median survival time=40.63 days, 5 μm microspheres median survival time=62.25 days), against 5-FU pure drug (median survival time=14.5 days). These results strongly suggest that 5-FU-loaded PLA microspheres increase life span of nude mice bearing MGC-803 tumors. After injection for 2 h, almost all the VEGF/5-FU loaded PLA nanoparticles could centralize at the human gastric cancer xenograft sites. That demonstrated VEGF monoclonal antibody remain its bioactivity after connection with nanoparticles, VEGF/5-FU loaded PLA nanoparticles had very exact targeting function for gastric tumor xenograft.
基金supported by a grant from the Korean Healthcare Technology R&D Project,Ministry for Health and Welfare Affairs,Republic of Korea(HI15C2558)。
文摘Particle shape has been recognized as one of the key properties of nanoparticles in biomedical applications including targeted drug delivery.Targeting ability of shape-engineered particles depends largely on targeting ligands conjugated on the particle surface.However,poor capacity for surface ligand conjugation remains a problem in anisotropic nanoparticles made with biodegradable polymers such as PLGA.In this study,we prepared anisotropic PLGA nanoparticles with abundant conjugatable surface functional groups by a film stretching-based fabrication method with poly(ethylene-alt-maleic acid)(PEMA).Scanning electron microscopy images showed that microrods and nanorods were successfully fabricated by the PEMA-based film stretching method.The presence of surface carboxylic acid groups was confirmed by confocal microscopy and zeta potential measurements.Using the improved film-stretching method,the amount of protein conjugated to the surface of nanorods was increased three-fold.Transferrin-conjugated,nanorods fabricated by the improved method exhibited higher binding and internalization than unmodified counterparts.Therefore,the PEMA-based film-stretching system presented in this study would be a promising fabrication method for non-spherical biodegradable polymeric micro-and nanoparticles with high capacity of surface modifications for enhanced targeted delivery.
文摘Venous and arterial thrombosis are closely related to many severe diseases, especially to cardiovascular and cerebrovasular disorders. Thrombolytic therapy has been proven to be an effective method to treat such disease, which decreased the mortality and morbidity greatly.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20110071130011)the National Science and Technology Major Project (No. 2012ZX09304004)
文摘The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.
文摘About 30% of human breast cancers are human epidermal growth factor receptor 2(HER2)+. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2+cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clinical outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the development of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional compartimentalization, which allows to combine the specific target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photothermal ablation or in photodynamic therapy have been functionalized in order to match specificity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2+breast cancer and anti-HER2 therapy, in particular deepening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted na-noparticles for HER2+ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical practice; however promising results encourage an upcoming translation of this research for the next future.
基金supported by the National Natural Science Foundation of China(22275073,22005119,21731002,2197510422150004)the Guangdong Major Project of Basic and Applied Research(2019B030302009)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2020A1515110404)the Guangzhou Basic and Applied Basic Research Foundation(2024A04J3597,202102020444)the Fundamental Research Funds for the Central Universities(21622409)。
文摘Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile attributes.Concurrently,magnetically actuated micro/nano-robots(MNRs)offer distinct advantages,such as untethered and precise manipulation.The fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug delivery.Here,we report a MOF-based magnetic microrobot swarm(MMRS)for targeted therapy.Our approach overcomes limitations associated with a single MNR,including limited drug loading and the risk of loss during manipulation.We select Zeolitic Imidazolate Framework-8(ZIF-8)as the drug vehicle for its superior loading potential and p H-sensitive decomposition.Our design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8,enabling collective behaviors under actuation.Tuning the yaw angle of alternating magnetic fields and nanoparticles'amount,the MMRSs with controllable size achieve instantaneous transformation among different configurations,including vortex-like swarms,chain-like swarms,and elliptical swarms,facilitating adaptation to environmental variations.Transported to the subcutaneous T24 tumor site,the MMRSs with encapsulated doxorubicin(DOX)automatically degrade and release the drug,leading to a dramatic reduction of the tumor in vivo.Our investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms,ushering in new avenues for accurate and non-invasive targeted drug delivery.
基金supported by the National Natural Science Foundation of China(31701561)。
文摘Edible plant derived exosome-like nanoparticles(ELNs)have been shown to have multiple nutraceutical functions.However,the diversity of plant materials makes the plant derived ELN study challenging.More efforts are still needed to explore the feasible isolation methods of edible plant derived ELNs and the possible roles of food-derived ELNs in improving human health.In this study,a size exclusion chromatography based method was compared with the traditional ultracentrifugation method to isolate blueberry derived ELNs(B-ELNs),and the miRNA profile of B-ELNs was analyzed by high-throughput sequencing.A total of 36 miRNAs were found to be enriched in B-ELNs compared with berry tissue,and their potential cross-kingdom human gene targets were further predicted.Results showed that size exclusion chromatography was effective for B-ELN isolation.The most abundant miRNAs in B-ELNs mainly belonged to the miR166 family and miR396 family.Target gene prediction indicated that B-ELNs could potentially regulate pathways related to the human digestive system,immune system and infectious diseases.
基金support from the Nuclear Regulatory Commission under Faculty Development Grant NRC-HQ-84-14-G-0052 and from the U.S.Department of Energy,Office of Science,Office of Basic Energy Sciences,Chemical Sciences,Geosciences,and Biosciences Division at LBNL under Contract DE-AC02-05CH11231,during the writing of this review.
文摘Radiotherapy,where ionizing radiation is locally delivered either through an external beam or by surgically implanting radionuclide-based seeds in the tumor,is one of the gold standard treatments for cancer.Due to the non-selective nature of radiation,healthy tissue surrounding the cancerous region is usually affected by the treatment.Hence,new strategies,including targeted alpha therapy,are being studied to improve the selectivity of the treatment and minimize side effects.Several challenges,however,limit the current development of targeted radiotherapy,such as the functionalization of the therapeutic agent with targeting vectors and controlling the release of recoiling daughters.Nanoparticles offer unique opportunities as drug delivery vehicles,since they are biocompatible,enhance the cellular uptake of drugs,and are easily functionalized with targeting molecules.In this review,we examine how nanoparticles can be used for targeted radiotherapy,either as sensitizers of external beams or as delivery vehicles for therapeutic radionuclides.We describe the clinical relevance of different types of nanoparticles,followed by an analysis of how these nanoconstructs can solve some of the main limitations of conventional radiotherapy.Finally,we critically discuss the current situation of nanoparticle-based radiotherapy in clinical settings and challenges that need to be overcome in the future for further development of the field.
基金supported in part by PA Tobacco Settlement Fund(Grant 4100062216,to C.D.,J.Y.J.C)support from the National Institutes of Health Award(AR072731,to J.Y.and EB026035,to X.L.)the National Science Foundation(NSF)Award(CBET-BME1330663,to C.D.)。
文摘Glioblastoma(GBM),the deadliest form of brain cancer,presents long-standing problems due to its localization.Chimeric antigen receptor(CAR)T cell immunotherapy has emerged as a powerful strategy to treat cancer.IL-13-receptor-α2(IL13Rα2),present in over 75%of GBMs,has been recognized as an attractive candidate for antiglioblastoma therapy.Here,we propose a novel multidisciplinary approach to target brain tumors using a combination of fluorescent,therapeutic nanoparticles and CAR T cells modified with a targeted-quadruplemutant of IL13(TQM-13)shown to have high binding affinity to IL13Rα2-expressing glioblastoma cells with low off-target toxicity.Azide-alkyne cycloaddition conjugation of nanoparticles to the surface of T cells allowed a facile,selective,and high-yielding clicking of the nanoparticles.Nanoparticles clicked onto T cells were retained for at least 8 days showing that the linkage is stable and promising a suitable time window for in vivo delivery.T cells clicked with doxorubicin-loaded nanoparticles showed a higher cytotoxic effect in vitro compared to bare T cells.In vitro and in vivo T cells expressing TQM-13 served as delivery shuttles for nanoparticles and significantly increased the number of nanoparticles reaching brain tumors compared to nanoparticles alone.This work represents a new platform to allow the delivery of therapeutic nanoparticles and T cells to solid tumors.
基金This work was supported by the National Natural Science Foundation of China(31971301,31971242,12032007)the China Postdoctoral Science Foundation(2020M673143)+1 种基金the Natural Science Foundation of Chongqing(cstc2020jcyj-bsh0025,cstc2019jcyj-zdxmX0028,cstc2017jcyjAX0186)Fundamental Research Funds for Central Universities(2020CDJQY-A061,2020CDJYGSX006,2019CDYGZD008,2018CDHB1B08)as well as the National‘111 Project’Base(B0625)are gratefully acknowledged.
文摘The development of nanomedicines provides new opportunities for the treatment of atherosclerosis(AS)due to their great advantages such as the improved drug solubility,enhanced bioavailability and reduced side effects.Despite these advantages,nanomedicines are still facing some challenges.The problems remain in the short circulation life,lack of specific targeting and poor drug release controllability.In order to overcome the shortages of conventional nanomedicines,the combination of biomimetic strategy with smart nanoagents has been proposed.In light with the high reactive oxygen species(ROS)level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS,we fabricated ROS-responsive biomimetic nanoparticles(NPs),which camouflaged macrophage membrane(MM)on ROS-responsive NPs loaded with rapamycin(RNPs)for potential application in AS therapy.The resulting ROSresponsive biomimetic NPs(MM/RNPs)exhibited favorable hydrodynamic size with negative surface charge,retained the functional proteins from MM,and showed ROS-responsive drug release.Because of the biomimetic camouflaging on surface,MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells.Meanwhile,MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro.Furthermore,the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation.Consequently,these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.
基金This work was supported by the Natural Science Foundation of Hubei Province(Grant No.2009HBKJH1).
文摘Superparamagnetic iron oxide(SPIO)nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility.A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles,such as surface-coated,targeted ligandconjugated,and/or drug-loaded SPIO nanoparticles,as powerful tools for targeted imaging and therapy.Moreover,the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment.In the present review,we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis,targeted therapy,and cancer imaging.
