In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a func...In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.展开更多
We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle pr...We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle properties of polymer nanoparticles were characterized by nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscope (SEM) and X-ray spectroscopy (EDX). Mesoporous materials were selected as the shell materials to encapsulate the smart core as the stable shell. The mesoporous shell was characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM). All the results showed that a well-defined core-shell structure with mesoporous structure was obtained, and this controllable delivery system will have the great potential in nanomedicine.展开更多
Water-soluble three-dimensional porous supramolecular organic frameworks（SOFs） have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery...Water-soluble three-dimensional porous supramolecular organic frameworks（SOFs） have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery systems（sof-DDSs） can adsorb dianionic pemetrexed（PMX）,a clinically used chemotherapeutic agent instantaneously upon dissolving in water,which is driven by both electrostatic attraction and hydrophobicity.The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells.Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells.Both in vitro and in vivo studies have revealed that sofDDSs considerably improve the treatment efficacy of PMX,leading to 6-12-fold reduction of the IC50 values,as compared with that of PMX alone.The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems展开更多
To assess the merits of PEGylated poly （lactic-co-glycolic acid） （PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be use...To assess the merits of PEGylated poly （lactic-co-glycolic acid） （PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol, DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with ^1H-NMR and FT-IR spectroscopy, and the molecular weight （MW） was determined by gel permeation chromatography. Fluorescent FITC-TNFR- BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency （EE） and the release of FITC-TNFR-BP in nanopartieles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than -20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.展开更多
Micro-and nano-fibers of shape memory polymers(SMP)offer multiple advantages like high specific surface area,poros-ity,and intelligence,and are suitable for biomedical applications.In this study,biodegradable poly(p-d...Micro-and nano-fibers of shape memory polymers(SMP)offer multiple advantages like high specific surface area,poros-ity,and intelligence,and are suitable for biomedical applications.In this study,biodegradable poly(p-dioxanone)(PPDO)materials were incorporated to improve the brittleness of shape memory polylactic acid(PLA),and plasticizers were used to reduce the transition temperature of SMP composites such that their transitions could be induced close to body temperature.Furthermore,an electrostatic spinning technology was applied to prepare SMP fibers with wrinkled structures and regulate their microstructures and morphologies such that the intelligent transition of wrinkled and smooth morphologies can be achieved on the fiber surface.The application of this controllable-morphology fiber membrane in intelligent controlled drug release and scar inhibition after Ahmed Glaucoma Valve(AGV)implantation was also studied.The drug release from the stretched and deformed drug-loaded fiber membranes was faster than those from membranes with the original shape.This membrane with micro-and nano-fibers had good anti-scarring effects that improved after drug loading.The achievement of intelligent controlled drug release and the evident anti-scarring effects of the membrane broaden the application of SMP fibers in the biomedical field.展开更多
The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying th...The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system.In this study,two kind of aqueous model drugs with different molecule weight,Congo red and albumin from bovine serum(BSA)were nanoencapsulated in poly(DL-lactic-co-glycolic acid)(PLGA)microspheres by emulsion electrospray.In the preparation process,the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution.The emulsion was then electrosprayed to fabricate drugnanoencapsulated PLGA microspheres.The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase(V_(w)/V_(o))and the molecule weight of model drugs.Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_(w)/V_(o).With the increase of the volume ratio of aqueous drug phase,the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate.Moreover,BSA showed a slower release rate from PLGA microspheres comparing to Congo red,which indicated the drug release rate could be affected by not only V_(w)/V_(o)but also the molecule weight of model drug.In brief,the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple systemto achieve controlled drug release at a desired rate satisfying the need of the practices.展开更多
Four-dimensional(4D)printing is a promising technology that provides solutions for compelling needs in various fields.Most of the reported 4D printed systems are based on the temporal shape transformation of printed s...Four-dimensional(4D)printing is a promising technology that provides solutions for compelling needs in various fields.Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects.Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing.Herein,we report a 4D printing approach using plant protein(zein)gel inspired by the amyloid fibrils formation mechanism.The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions.The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading,faster drug release and degradation than those printed in the supporting bath with lower water content.Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system.4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model.Overall,this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.展开更多
This report describes the design and synthesis of gold nanostars(AuNSs) containing liposomes by the in situ reduction of gold precursor,HAuCU(pre-encapsulated within the liposomes) through HEPES diffusion and reductio...This report describes the design and synthesis of gold nanostars(AuNSs) containing liposomes by the in situ reduction of gold precursor,HAuCU(pre-encapsulated within the liposomes) through HEPES diffusion and reduction.Compared with the conventional process that encapsulates the pre-synthesized gold nanoparticles into liposomes during the thin-film hydration step,this facile and convenient method allows the formation and simultaneous encapsulation of AuNSs within liposomes.The absorption spectra of AuNSs can be tuned between visible and near infra-red(NIR) regions by controlling the size and morphology of AuNSs through varying the concentrations of HAuCU and HEPES.As a proof of concept,we demonstrate the synthesis of AuNSs with a maximum absorbance at 803 nm within the temperature-sensitive liposomes.These liposomes can produce stronger photoacoustic signals(1.5 fold) in the NIR region than blood.Furthermore,when there are drugs(i.e.,doxorubicin) within these liposomes,the irradiation with the NIR pulse laser will disrupt the liposomes and trigger the 100%release of these pre-encapsulated drugs within 10 seconds.In comparison,there is neglectable contrast enhancement or minor release(10%) of drugs for the pure liposomes under the same conditions.Finally,cell experiment shows the potential therapeutic application of this system.展开更多
A set of amphiphilic poly（ethylene glycol）-b-poly（ethylene brassylate）（PEG-b-PEB） copolymers based on the PEB hydrophobic block was first synthesized by ring-opening polymerization of ethylene brassylate with an...A set of amphiphilic poly（ethylene glycol）-b-poly（ethylene brassylate）（PEG-b-PEB） copolymers based on the PEB hydrophobic block was first synthesized by ring-opening polymerization of ethylene brassylate with an organic catalyst. The EB/PEG molar ratios and reaction times were adjusted to achieve different chain lengths of PEB. Block copolymers that were characterized by1 H NMR and GPC could selfassemble into multimorphological aggregates in aqueous solution, which were characterized by DLS and TEM. The hydrophobic doxorubicin（DOX） was chosen as a drug model and successfully encapsulated into the nanoparticles. The release kinetics of DOX were investigated.展开更多
Four water-soluble porous supramolecular organic framework drug delivery systems（sof-DDSs） have been used to adsorb doxorubicin（DOX） in water at physiological pH of 7.4,which is driven exclusively by hydrophobicit...Four water-soluble porous supramolecular organic framework drug delivery systems（sof-DDSs） have been used to adsorb doxorubicin（DOX） in water at physiological pH of 7.4,which is driven exclusively by hydrophobicity.The resulting complexes DOX@SOFs are formed instantaneously upon dissolving the components in water.The drug-adsorbed sof-DDSs can undergo plasm circulation with important maintenance of the drug and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells.DOX is released readily in the cancer cells due to the protonation of its amino group in the acidic medium of cancer cells.In vitro and in vivo experiments reveal that the delivery of SOF-a-d remarkably improve the cytotoxicity of DOX for the MCF-7/Adr cells and tumors,leading to 13-19-fold reduction of the 1C_（50）values as compared with that of DOX.This new sof-DDSs strategy omits the indispensable loading process required by most of reported nano-scaled carriers for neutral hydrophobic chemotherapeutic agents,and thus should be highly valuable for future development of low-cost delivery systems.展开更多
The utilization of poly （2-hydroxyethylmetha- crylate） grafted agar （Ag-g-P（HEMA）） as a matrix for the controlled release of 5-aminosalicylic acid was investi- gated. Grafted copolymers of 2-hydroxyethylmethacry...The utilization of poly （2-hydroxyethylmetha- crylate） grafted agar （Ag-g-P（HEMA）） as a matrix for the controlled release of 5-aminosalicylic acid was investi- gated. Grafted copolymers of 2-hydroxyethylmethacrylate （HEMA） monomers on agar were synthesized by micro- wave assisted method. In vitro drug release studies were performed at pH values of 2 and 7 in order to investigate the possibility of pH triggered release for colon targeted drug delivery. Further, the percent grafting vs. tso （the time taken for release of 50% of the enclosed drug） value was studied and the results indicate that it may be possible to develop a programmable drug release matrix based on grafted polysaccharide. Ag-g-P（HEMA） appears to be a useful matrix for controlled release.展开更多
Although intelligent hydrogels have shown bright potential application in biomedical fields,they were prepared by conventional methods and still face many serious challenges,such as uncontrollable stimulus-response an...Although intelligent hydrogels have shown bright potential application in biomedical fields,they were prepared by conventional methods and still face many serious challenges,such as uncontrollable stimulus-response and low response sensitivity.Recently,RAFT polymerization provides a versatile strategy for the fabrication of intelligent hydrogels with improved stimulus-response properties,owing to the ability to efficiently construct hydrogel precursors with well-defined structure,such as block copolymer,graft copolymer,star copolymer.In this review,we summarized the recent progress on intelligent hydrogels based on RAFT polymerization with emphasis on their fabrication strategies and applications for controlled drug delivery.展开更多
Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldru...Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldrug and encapsulate within folic acid modified carboxymethylchitosan（FACMCS）nanoparticles through self-assembling.The chemicalstructure,morphology,release and targeting of nanoparticles were characterized by routine detection.It is demonstrated that the mean diameter is about 150 nm,the release rate increases with the decreasing of p H,the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5：2,and nanoparticles can effectively bind onto HL60 cells in vitro.The experimentalresults indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potentialp Hsensitive drug delivery system with leukemic targeting properties.展开更多
Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases,and can improve therapeutic effectiveness as well as alleviate side effects in patients.In this wor...Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases,and can improve therapeutic effectiveness as well as alleviate side effects in patients.In this work,a pH and H_(2)O_(2)-responsive drug delivery platform with high doxorubicin(DOX)loading capacity has been established through coordination interaction between DOX and phenylboronic acid containing block polymer.A composited drug nanocarrier is further fabricated by growing a zeolitic imidazolate framework 8(ZIF-8)on the surface of drug-loaded polymer micelles.The study verifies that ZIF-8 shell can act as intelligent“switch”to prevent DOX leaking from core–shell nanoparticles upon H_(2)O_(2) stimulus.However,a burst drug release is detected upon pH and H_(2)O_(2) stimuli due to the further disassociation of ZIF-8 in acid solution.Moreover,the in vitro anti-cancer experiments demonstrate that the DOX-loaded core–shell nanoparticles provide effective treatment towards cancer cells but have negligible effect on normal cells,which results from the high concentration of H_(2)O_(2) and low pH in the microenvironment of tumor cells.展开更多
In different parts of the gastrointestinal tract, the rate of drug release from polyelectrolyte hydrogel tablets is highly affected by variance of ionic concentration. This research aims at revealing clearly how the d...In different parts of the gastrointestinal tract, the rate of drug release from polyelectrolyte hydrogel tablets is highly affected by variance of ionic concentration. This research aims at revealing clearly how the drug release from a hydrogel matrix is affected by ionic concentration of external solution through the finite element simulation and triphasic mechanism model. The coupled relationship of the motions including the polyelectrolyte hydrogel swelling, the water flow and the ion diffusion, is illustrated in the present work. In order to simulate the drug controlled release from a swollen polyelectrolyte hydrogel carrier, the mathematical model was built on the basis of the multiphasic theory of polyelectrolyte hydrogels. Finally, the reliability of the simulation method was verified qualitatively by experimental results. The results reveal that when the initial concentration of fixed anions of polymer network is higher than the concentration of free anions in the external solution, the drug release rate increases with increasing the ionic concentration of the external solution. The research is helpful for the optimal design of oral drug release in gastrointestinal tract.展开更多
Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the ...Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the DOX-loaded polyvinyl alcohol( PVA)hydrogel was prepared by freeze-thawing technique. The swelling test and the mechanical properties of the pure PVA hydrogels were performed. In addition, the in vitro drug release profiles were examined and the in vitro antitumor efficiency against He La cells was also estimated. The results indicated that the resulting PVA hydrogels contained significant amounts of water and possessed good mechanical properties,and DOX-loaded PVA hydrogel exhibited a sustained and p H-responsive DOX release. The MTT assays also demonstrated that the released DOX could effectively inhibit the proliferation of He La cells. Thus,the cross-linked PVA hydrogel can be further developed as a promising platform for cancer therapy.展开更多
Microneedles are considered to be an effective,convenient,non-invasive,biosafety and compliant medical technology for vaccinations,biomarker testing,medical aesthetics and other related fields.Nonetheless,further clin...Microneedles are considered to be an effective,convenient,non-invasive,biosafety and compliant medical technology for vaccinations,biomarker testing,medical aesthetics and other related fields.Nonetheless,further clinical and commercial translation of regular microneedles is hampered by challenges in manufacturability,cost variability,insufficient comfort,contamination and so on.Recent innovations in functional biomaterials and chemical engineering technologies have been applied to develop extensible and swellable hydrogel-forming microneedles,achieving precise and controlled drug delivery and localized sampling from the target tissues.In this review,we systematically summarize the latest development of the extensible and swellable hydrogel-forming microneedles,including deep point-of-care testing,drug deployment,wound healing and mucoadhesion improvement.In addition,further analysis of the challenges and prospects for clinical application of current strategies is well presented.It is believed that the combined efforts of engineering,material,pharmaceutical and clinical research will contribute to the future success of this clinical and commercial translation.展开更多
Owing to their high significance in fundamental study and diverse applications,stimuli-responsive and fluorescent polymers,particularly those with cluster-triggered emission(CTE)featured by non-conjugated chromophores...Owing to their high significance in fundamental study and diverse applications,stimuli-responsive and fluorescent polymers,particularly those with cluster-triggered emission(CTE)featured by non-conjugated chromophores,have drawn tremendous attention in recent years.In this work,fluorescent and multi-responsive polysiloxane(FRPS)was synthesized by hydrolytic condensation polymerization of 3-aminopropyl methyl diethoxysilane(APMS)with 3-(N-isopropyl propionamide)iminopropyl methyl diethoxysilane(APMS-NIP),which was formed in situ through aza-Michael addition between APMS and N-isopropyl acrylamide.FRPS was not only highly sensitive to temperature,pH and CO_(2) in water,but also showed an enhanced and stimuli-adjustable fluorescence emission.The effects of monomer feeding,pH and CO_(2) on its lower critical solution temperature and fluorescent property were investigated.FRPS fluorescence emission was ascribed to CTE mechanism.In addition,FRPS was shown to be highly potential as physiological indicator for cell imaging,and for controlled release and trace detection of doxorubicin.This study provides therefore a type of stimuli-responsive and fluorescent material for potential applications in biomedical fields,and it is also of great significance for understanding of the fluorescence mechanism of polysiloxane-based stimuli-responsive polymers.展开更多
Non-aromatic fluorescent and multi-responsive materials,exhibiting inherent fluorescence emission and controlled phase change,have garnered significant attention in recent years.However,the underlying interaction betw...Non-aromatic fluorescent and multi-responsive materials,exhibiting inherent fluorescence emission and controlled phase change,have garnered significant attention in recent years.However,the underlying interaction between their fluorescent properties and phase transition remains unclear.In this study,we synthesized a series of catalyst-free aza-Michael addition-based polyethyleneimine(RFPEI)materials by reacting polyethyleneimine(PEI)with N-isopropyl acrylamide(NIPAM).The resulting RFPEI was comprehensively characterized,and demonstrated dual-phase transition behavior(LCST and UCST)in water,which could be finely tuned by adjusting its composition or external factors such as pH.Notably,upon UV irradiation(365 nm),RFPEI exhibited strong fluorescence emission.We further investigated the effects of NIPAM grafting percentage to PEI,polymer concentration,and pH on the LCST/UCST and fluorescent properties of RFPEI aqueous solutions.Moreover,we showcased the great potential of RFPEI as a versatile tool for physiological cell imaging,trace detection,and controlled release of doxorubicin.Our study presents a novel class of stimuli-responsive fluorescent materials with promising applications in the field of biomedicine.展开更多
基金supported by the Chinese Natural Science Foundation Project (Grant No. 30970784 and 81171455)a National Distinguished Young Scholars Grant (Grant No. 31225009) from the National Natural Science Foundation of China+5 种基金the National Key Basic Research Program of China (Grant No. 2009CB930200)the Chinese Academy of Sciences (CAS) ‘Hundred Talents Program’ (Grant No. 07165111ZX)the CAS Knowledge Innovation Program, and the State HighTech Development Plan (Grant No. 2012AA020804)the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (Grant No. XDA09030301)NIH/NIMHD 8 G12 MD007597USAMRMC W81XWH-10-1-0767 grants
文摘In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.
基金Funded by National Natural Science Foundation of China (Nos.51861135313,U1663225,U1662134,21711530705,21673282,21473246)Fundamental Research Funds for the Central Universities (Nos.19lgpy112,19lgzd16,2019IB005)+3 种基金National Key R&D Program of China (No.2017YFC1103800)Program for Changjiang Scholars and Innovative Research Team in University (No.IRT_15R52)International Science&Technology Cooperation Program of China (No.2015DFE52870)Jilin Province Science and Technology Development Plan (No.20180101208JC)
文摘We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle properties of polymer nanoparticles were characterized by nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscope (SEM) and X-ray spectroscopy (EDX). Mesoporous materials were selected as the shell materials to encapsulate the smart core as the stable shell. The mesoporous shell was characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM). All the results showed that a well-defined core-shell structure with mesoporous structure was obtained, and this controllable delivery system will have the great potential in nanomedicine.
基金the National Natural Science Foundation of China(Nos.21432004,21529201,and 91527301)the Ministry of Science and Technology of China(No.2013CB834501)+1 种基金the Ministry of Education of China Research Fund for the Doctoral Program and of China for financial supportsupport from the Molecular Foundry,Lawrence Berkeley National Laboratory,supported by the Office of Science,Office of Basic Energy Sciences,Scientific User Facilities Division,of the U.S.Department of Energy under Contract No.DE-AC02-05CH11231
文摘Water-soluble three-dimensional porous supramolecular organic frameworks（SOFs） have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery systems（sof-DDSs） can adsorb dianionic pemetrexed（PMX）,a clinically used chemotherapeutic agent instantaneously upon dissolving in water,which is driven by both electrostatic attraction and hydrophobicity.The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells.Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells.Both in vitro and in vivo studies have revealed that sofDDSs considerably improve the treatment efficacy of PMX,leading to 6-12-fold reduction of the IC50 values,as compared with that of PMX alone.The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems
基金Funded by the National 863 Project of China (No. 2004AA215162)
文摘To assess the merits of PEGylated poly （lactic-co-glycolic acid） （PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol, DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with ^1H-NMR and FT-IR spectroscopy, and the molecular weight （MW） was determined by gel permeation chromatography. Fluorescent FITC-TNFR- BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency （EE） and the release of FITC-TNFR-BP in nanopartieles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than -20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.
基金supported by the National Natural Science Foundation of China(Grant No.11802075,12072094,81870654,and 82070956)the Fundamental Research Funds for the Central Universities(No.IR2021106 and IR2021232)Applied Technology Research and Development Program of Heilongjiang Provincial Science and Technology Department(GA20C008).
文摘Micro-and nano-fibers of shape memory polymers(SMP)offer multiple advantages like high specific surface area,poros-ity,and intelligence,and are suitable for biomedical applications.In this study,biodegradable poly(p-dioxanone)(PPDO)materials were incorporated to improve the brittleness of shape memory polylactic acid(PLA),and plasticizers were used to reduce the transition temperature of SMP composites such that their transitions could be induced close to body temperature.Furthermore,an electrostatic spinning technology was applied to prepare SMP fibers with wrinkled structures and regulate their microstructures and morphologies such that the intelligent transition of wrinkled and smooth morphologies can be achieved on the fiber surface.The application of this controllable-morphology fiber membrane in intelligent controlled drug release and scar inhibition after Ahmed Glaucoma Valve(AGV)implantation was also studied.The drug release from the stretched and deformed drug-loaded fiber membranes was faster than those from membranes with the original shape.This membrane with micro-and nano-fibers had good anti-scarring effects that improved after drug loading.The achievement of intelligent controlled drug release and the evident anti-scarring effects of the membrane broaden the application of SMP fibers in the biomedical field.
基金This work is partly supported by Tsinghua University Initiative Scientific Research Program(20161080091,20131089199)China Postdoctoral Science Foundation(No.2016M591075)the National Natural Science Foundation of China(51572144).
文摘The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system.In this study,two kind of aqueous model drugs with different molecule weight,Congo red and albumin from bovine serum(BSA)were nanoencapsulated in poly(DL-lactic-co-glycolic acid)(PLGA)microspheres by emulsion electrospray.In the preparation process,the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution.The emulsion was then electrosprayed to fabricate drugnanoencapsulated PLGA microspheres.The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase(V_(w)/V_(o))and the molecule weight of model drugs.Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_(w)/V_(o).With the increase of the volume ratio of aqueous drug phase,the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate.Moreover,BSA showed a slower release rate from PLGA microspheres comparing to Congo red,which indicated the drug release rate could be affected by not only V_(w)/V_(o)but also the molecule weight of model drug.In brief,the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple systemto achieve controlled drug release at a desired rate satisfying the need of the practices.
基金This study was supported by the National Key R&D Program of China(2019YFE0101200)the Science and Technology Commission Shanghai Municipality,China(13JC1403400,18490740200)+1 种基金the Foreign Young Talent Program from the Ministry of Science and Technology,China(QN2022134003L)the Plan of Jiaxing Innovation and Elites Leading,China.
文摘Four-dimensional(4D)printing is a promising technology that provides solutions for compelling needs in various fields.Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects.Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing.Herein,we report a 4D printing approach using plant protein(zein)gel inspired by the amyloid fibrils formation mechanism.The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions.The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading,faster drug release and degradation than those printed in the supporting bath with lower water content.Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system.4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model.Overall,this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.
基金supported by NTU-Northwestern Institute for Nanomedicine(To Xu CJ)the Tier-2 Grant funded by the Ministry of Education in Singapore(ARC2/15:M4020238 to M.R)
文摘This report describes the design and synthesis of gold nanostars(AuNSs) containing liposomes by the in situ reduction of gold precursor,HAuCU(pre-encapsulated within the liposomes) through HEPES diffusion and reduction.Compared with the conventional process that encapsulates the pre-synthesized gold nanoparticles into liposomes during the thin-film hydration step,this facile and convenient method allows the formation and simultaneous encapsulation of AuNSs within liposomes.The absorption spectra of AuNSs can be tuned between visible and near infra-red(NIR) regions by controlling the size and morphology of AuNSs through varying the concentrations of HAuCU and HEPES.As a proof of concept,we demonstrate the synthesis of AuNSs with a maximum absorbance at 803 nm within the temperature-sensitive liposomes.These liposomes can produce stronger photoacoustic signals(1.5 fold) in the NIR region than blood.Furthermore,when there are drugs(i.e.,doxorubicin) within these liposomes,the irradiation with the NIR pulse laser will disrupt the liposomes and trigger the 100%release of these pre-encapsulated drugs within 10 seconds.In comparison,there is neglectable contrast enhancement or minor release(10%) of drugs for the pure liposomes under the same conditions.Finally,cell experiment shows the potential therapeutic application of this system.
基金supported by the Open Fund of State Key Laboratory of Medicinal Chemical Biology (Nankai University) under grant 20140523the Fundamental Research Funds for the Central Universities (Nos. SWU 113075 and XDJK2014B015)
文摘A set of amphiphilic poly（ethylene glycol）-b-poly（ethylene brassylate）（PEG-b-PEB） copolymers based on the PEB hydrophobic block was first synthesized by ring-opening polymerization of ethylene brassylate with an organic catalyst. The EB/PEG molar ratios and reaction times were adjusted to achieve different chain lengths of PEB. Block copolymers that were characterized by1 H NMR and GPC could selfassemble into multimorphological aggregates in aqueous solution, which were characterized by DLS and TEM. The hydrophobic doxorubicin（DOX） was chosen as a drug model and successfully encapsulated into the nanoparticles. The release kinetics of DOX were investigated.
基金the National Natural Science Foundation of China (Nos.21432004,21529201,91527301)the Ministry of Science and Technology of China(No.2013CB834501)+1 种基金the Ministry of Education of China Research Fund for the Doctoral Program and of China for financial supportsupport from the Molecular Foundry,Lawrence Berkeley National Laboratory,supported by the Office of Science,Office of Basic Energy Sciences,Scientific User Facilities Division,of the U.S.Department of Energy under Contract No.DE-AC0205CH11231
文摘Four water-soluble porous supramolecular organic framework drug delivery systems（sof-DDSs） have been used to adsorb doxorubicin（DOX） in water at physiological pH of 7.4,which is driven exclusively by hydrophobicity.The resulting complexes DOX@SOFs are formed instantaneously upon dissolving the components in water.The drug-adsorbed sof-DDSs can undergo plasm circulation with important maintenance of the drug and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells.DOX is released readily in the cancer cells due to the protonation of its amino group in the acidic medium of cancer cells.In vitro and in vivo experiments reveal that the delivery of SOF-a-d remarkably improve the cytotoxicity of DOX for the MCF-7/Adr cells and tumors,leading to 13-19-fold reduction of the 1C_（50）values as compared with that of DOX.This new sof-DDSs strategy omits the indispensable loading process required by most of reported nano-scaled carriers for neutral hydrophobic chemotherapeutic agents,and thus should be highly valuable for future development of low-cost delivery systems.
文摘The utilization of poly （2-hydroxyethylmetha- crylate） grafted agar （Ag-g-P（HEMA）） as a matrix for the controlled release of 5-aminosalicylic acid was investi- gated. Grafted copolymers of 2-hydroxyethylmethacrylate （HEMA） monomers on agar were synthesized by micro- wave assisted method. In vitro drug release studies were performed at pH values of 2 and 7 in order to investigate the possibility of pH triggered release for colon targeted drug delivery. Further, the percent grafting vs. tso （the time taken for release of 50% of the enclosed drug） value was studied and the results indicate that it may be possible to develop a programmable drug release matrix based on grafted polysaccharide. Ag-g-P（HEMA） appears to be a useful matrix for controlled release.
基金supported by National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2018ZX10301402)International Cooperation and Exchange of the National Natural Science Foundation of China (No. 51820105004)+2 种基金the Science and Technology Program of Guangzhou (No. 201707010094)Guangdong Innovative and Entrepreneurial Research Team Program (Nos. 2013S086 and 2016ZT06S029)the Science and Technology Planning Project of Shenzhen (No. JCYJ20170307141438157)
文摘Although intelligent hydrogels have shown bright potential application in biomedical fields,they were prepared by conventional methods and still face many serious challenges,such as uncontrollable stimulus-response and low response sensitivity.Recently,RAFT polymerization provides a versatile strategy for the fabrication of intelligent hydrogels with improved stimulus-response properties,owing to the ability to efficiently construct hydrogel precursors with well-defined structure,such as block copolymer,graft copolymer,star copolymer.In this review,we summarized the recent progress on intelligent hydrogels based on RAFT polymerization with emphasis on their fabrication strategies and applications for controlled drug delivery.
基金Funded by the National Natural Science Foundation of China(No.50973088)
文摘Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldrug and encapsulate within folic acid modified carboxymethylchitosan（FACMCS）nanoparticles through self-assembling.The chemicalstructure,morphology,release and targeting of nanoparticles were characterized by routine detection.It is demonstrated that the mean diameter is about 150 nm,the release rate increases with the decreasing of p H,the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5：2,and nanoparticles can effectively bind onto HL60 cells in vitro.The experimentalresults indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potentialp Hsensitive drug delivery system with leukemic targeting properties.
基金financially supported by the Natural Science Foundation of Zhejiang Province(No.LY20E030005)。
文摘Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases,and can improve therapeutic effectiveness as well as alleviate side effects in patients.In this work,a pH and H_(2)O_(2)-responsive drug delivery platform with high doxorubicin(DOX)loading capacity has been established through coordination interaction between DOX and phenylboronic acid containing block polymer.A composited drug nanocarrier is further fabricated by growing a zeolitic imidazolate framework 8(ZIF-8)on the surface of drug-loaded polymer micelles.The study verifies that ZIF-8 shell can act as intelligent“switch”to prevent DOX leaking from core–shell nanoparticles upon H_(2)O_(2) stimulus.However,a burst drug release is detected upon pH and H_(2)O_(2) stimuli due to the further disassociation of ZIF-8 in acid solution.Moreover,the in vitro anti-cancer experiments demonstrate that the DOX-loaded core–shell nanoparticles provide effective treatment towards cancer cells but have negligible effect on normal cells,which results from the high concentration of H_(2)O_(2) and low pH in the microenvironment of tumor cells.
文摘In different parts of the gastrointestinal tract, the rate of drug release from polyelectrolyte hydrogel tablets is highly affected by variance of ionic concentration. This research aims at revealing clearly how the drug release from a hydrogel matrix is affected by ionic concentration of external solution through the finite element simulation and triphasic mechanism model. The coupled relationship of the motions including the polyelectrolyte hydrogel swelling, the water flow and the ion diffusion, is illustrated in the present work. In order to simulate the drug controlled release from a swollen polyelectrolyte hydrogel carrier, the mathematical model was built on the basis of the multiphasic theory of polyelectrolyte hydrogels. Finally, the reliability of the simulation method was verified qualitatively by experimental results. The results reveal that when the initial concentration of fixed anions of polymer network is higher than the concentration of free anions in the external solution, the drug release rate increases with increasing the ionic concentration of the external solution. The research is helpful for the optimal design of oral drug release in gastrointestinal tract.
基金National Natural Science Foundation of China(No.31271028)Shanghai Nano Science Program,China(No.11nm0505500)+1 种基金Innovation Program of Shanghai M unicipal Education Commission,China(No.13ZZ051)Chinese Universities Scientific Fund,China(No.EG2014023)
文摘Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the DOX-loaded polyvinyl alcohol( PVA)hydrogel was prepared by freeze-thawing technique. The swelling test and the mechanical properties of the pure PVA hydrogels were performed. In addition, the in vitro drug release profiles were examined and the in vitro antitumor efficiency against He La cells was also estimated. The results indicated that the resulting PVA hydrogels contained significant amounts of water and possessed good mechanical properties,and DOX-loaded PVA hydrogel exhibited a sustained and p H-responsive DOX release. The MTT assays also demonstrated that the released DOX could effectively inhibit the proliferation of He La cells. Thus,the cross-linked PVA hydrogel can be further developed as a promising platform for cancer therapy.
基金supported by the Fundamental Research Funds for the Central Universities(No.5003510106)the National Natural Science Foundation of China(Nos.U21A20417,31930067)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18002)。
文摘Microneedles are considered to be an effective,convenient,non-invasive,biosafety and compliant medical technology for vaccinations,biomarker testing,medical aesthetics and other related fields.Nonetheless,further clinical and commercial translation of regular microneedles is hampered by challenges in manufacturability,cost variability,insufficient comfort,contamination and so on.Recent innovations in functional biomaterials and chemical engineering technologies have been applied to develop extensible and swellable hydrogel-forming microneedles,achieving precise and controlled drug delivery and localized sampling from the target tissues.In this review,we systematically summarize the latest development of the extensible and swellable hydrogel-forming microneedles,including deep point-of-care testing,drug deployment,wound healing and mucoadhesion improvement.In addition,further analysis of the challenges and prospects for clinical application of current strategies is well presented.It is believed that the combined efforts of engineering,material,pharmaceutical and clinical research will contribute to the future success of this clinical and commercial translation.
基金This work was financially supported by Nature Science Foundation of Shandong Province,China(Nos.ZR2021MB112 and ZR2022MB051)Science and Technology Bureau of Jinan City(No.2021GXRC105)+1 种基金Postdoctoral Science Foundation of China(No.2022M712343)as well as by Basic and Applied Basic Research Foundation(No.2020A1515110374)of Guangdong Province,China.
文摘Owing to their high significance in fundamental study and diverse applications,stimuli-responsive and fluorescent polymers,particularly those with cluster-triggered emission(CTE)featured by non-conjugated chromophores,have drawn tremendous attention in recent years.In this work,fluorescent and multi-responsive polysiloxane(FRPS)was synthesized by hydrolytic condensation polymerization of 3-aminopropyl methyl diethoxysilane(APMS)with 3-(N-isopropyl propionamide)iminopropyl methyl diethoxysilane(APMS-NIP),which was formed in situ through aza-Michael addition between APMS and N-isopropyl acrylamide.FRPS was not only highly sensitive to temperature,pH and CO_(2) in water,but also showed an enhanced and stimuli-adjustable fluorescence emission.The effects of monomer feeding,pH and CO_(2) on its lower critical solution temperature and fluorescent property were investigated.FRPS fluorescence emission was ascribed to CTE mechanism.In addition,FRPS was shown to be highly potential as physiological indicator for cell imaging,and for controlled release and trace detection of doxorubicin.This study provides therefore a type of stimuli-responsive and fluorescent material for potential applications in biomedical fields,and it is also of great significance for understanding of the fluorescence mechanism of polysiloxane-based stimuli-responsive polymers.
基金supported by Nature Science Foundation of Shandong Province,China(Nos.ZR2021MB112 and ZR2022MB051)Science and Technology Bureau of Jinan City(2021GXRC105)+1 种基金Postdoctoral Science Foundation of China(2022M712343)as well as by Basic and Applied Basic Research Foundation(2020A1515110374)of Guangdong Province,China.
文摘Non-aromatic fluorescent and multi-responsive materials,exhibiting inherent fluorescence emission and controlled phase change,have garnered significant attention in recent years.However,the underlying interaction between their fluorescent properties and phase transition remains unclear.In this study,we synthesized a series of catalyst-free aza-Michael addition-based polyethyleneimine(RFPEI)materials by reacting polyethyleneimine(PEI)with N-isopropyl acrylamide(NIPAM).The resulting RFPEI was comprehensively characterized,and demonstrated dual-phase transition behavior(LCST and UCST)in water,which could be finely tuned by adjusting its composition or external factors such as pH.Notably,upon UV irradiation(365 nm),RFPEI exhibited strong fluorescence emission.We further investigated the effects of NIPAM grafting percentage to PEI,polymer concentration,and pH on the LCST/UCST and fluorescent properties of RFPEI aqueous solutions.Moreover,we showcased the great potential of RFPEI as a versatile tool for physiological cell imaging,trace detection,and controlled release of doxorubicin.Our study presents a novel class of stimuli-responsive fluorescent materials with promising applications in the field of biomedicine.
基金financially supported by the National Natural Science Foundation of China(52371248)National Key R&D Program of China(2021YFB3802200)+5 种基金Guangdong Basic and Applied Basic Research Foundation(2023A1515010905)he Scientific and Technological Innovation Foundation of Shunde Graduate School,USTB(BK22BE012)the funding supports from Singapore Ministry of Education(AcRF Tier 1 RS13/20 and RG4/21)A*STAR Singapore(AME YIRG A2084c0158)the Center of Hydrogen Innovation,National University of Singapore(CHI-P2022-05)Nanyang Technological University Startup Grants。
