The abuse of plastic food packaging has brought about severe white pollution issues around the world.Developing green and sustainable biomass packaging is an effective way to solve this problem.Hence,a chitosan/sodium...The abuse of plastic food packaging has brought about severe white pollution issues around the world.Developing green and sustainable biomass packaging is an effective way to solve this problem.Hence,a chitosan/sodium alginate-based multilayer film is fabricated via a layer-by-layer(LBL)self-assembly method.With the help of superior interaction between the layers,the multilayer film possesses excellent mechanical properties(with a tensile strength of 50 MPa).Besides,the film displays outstanding water retention property(blocking moisture of 97.56%)and ultraviolet blocking property.Anthocyanin is introduced into the film to detect the food quality since it is one natural plant polyphenol that is sensitive to the pH changes ranging from 1 to 13 in food when spoilage occurs.It is noted that the film is also bacteriostatic which is desired for food packaging.This study describes a simple technique for the development of advanced multifunctional and fully biodegradable food packaging film and it is a sustainable alternative to plastic packaging.展开更多
Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,a...Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.展开更多
Positively charged composite nanofiltration （NF） membranes were prepared through interfacial polymerization of poly[2-（N,N-dimethyl amino）ethyl methacrylate]（PDMAEMA） on porous polysulfone （PSF） substrate memb...Positively charged composite nanofiltration （NF） membranes were prepared through interfacial polymerization of poly[2-（N,N-dimethyl amino）ethyl methacrylate]（PDMAEMA） on porous polysulfone （PSF） substrate membranes. The effects of pH on swelling ratio （SR） of the pure crosslinked PDMAEMA membrane and on separation performances of the composite NF membrane were investigated. The results show that the quaternized amino groups produced through interfacial polymerization technique are soluble in both phases, which accelerate the crosslinking reaction as self-catalysts. The swelling/contracting behavior of the pure crosslinked PDMAEMA exhibited a well reversible pH sensitive property. Importantly, the rejection and flux of the composite NF membrane show pH-sensitive behavior in NF process. Furthermore, with the help of a relatively novel method to measure membrane conduction, the true zeta potentials calculated on the basis of the streaming potential measurements proved the pH-sensitive behavior of the NF membrane.展开更多
A novel pH-sensitive complex was prepared by using oxidized konjac glucomannan and 4-aminosalicylic acid （4-ASA） through glutaraldehyde as a cross-linking agent. The product was characterized by FTIR and 13C NMR spe...A novel pH-sensitive complex was prepared by using oxidized konjac glucomannan and 4-aminosalicylic acid （4-ASA） through glutaraldehyde as a cross-linking agent. The product was characterized by FTIR and 13C NMR spectra, and the thermogravimetric analysis was also studied. The drug release studies in vitro showed that the amount of 4-ASA released from the complex was about 4%, 56% and 17% after 12 h at pH 1.2, 6.8 and 7.4, respectively. The data demonstrate that the rate of the drug release of the complex can be more effectively controlled by pH value. The results showed that the novel pH-sensitive complex could be potentially useful for colon-targeting drug delivery system.展开更多
Most of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy.Based on physiological differences between the normal tissue an...Most of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy.Based on physiological differences between the normal tissue and the tumor tissue,one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery systems.The copolymers with reversible protonationedeprotonation core units or acid-liable bonds between the therapeutic agents and the micelle-forming copolymers can be used to form pH-sensitive polymeric micelles for extracellular and intracellular drug smart release.These systems can be triggered to release drug in response to the slightly acidic extracellular fluids of tumor tissue after accumulation in tumor tissues via the enhanced permeability and retention effect,or they can be triggered to release drug in endosomes or lysosomes by pH-controlled micelle hydrolysis or dissociation after uptake by cells via the endocytic pathway.The pH-sensitive micelles have been proved the specific tumor cell targeting,enhanced cellular internalization,rapid drug release,and multidrug resistance reversal.The multifunctional polymeric micelles combining extracellular pH-sensitivity with receptor-mediated active targeting strategies are of great interest for enhanced tumor targeting.The micelles with receptor-mediated and intracellular pH targeting functions are internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells,which reverses multidrug resistance.The pH sensitivity strategy of the polymeric micelles facilitates the specific drug delivery with reduced systemic side effects and improved chemotherapeutical efficacy,and is a novel promising platform for tumor-targeting drug delivery.展开更多
The combination of Ce6,an acknowledged photosensitizer,and TPL,a natural anticancer agent,has been demonstrated as a useful strategy to reinforce the tumor growth suppression,as well as decrease the systemic side effe...The combination of Ce6,an acknowledged photosensitizer,and TPL,a natural anticancer agent,has been demonstrated as a useful strategy to reinforce the tumor growth suppression,as well as decrease the systemic side effects compared with their monotherapy.However,in view of the optimal chemo-photodynamic combination efficiency,there is still short of the feasible nanovehicle to steadily co-deliver Ce6 and TPL,and stimuli-responsively burst release drugs in tumor site.Herein,we described the synergistic antitumor performance of a pH-sensitive supramolecular nanosystem,mediated by the host–guest complexing betweenβ-CD and acid pH-responsive amphiphilic co-polymer mPEG-PBAE-mPEG,showing the shell–core structural micelles with the tightβ-CD layer coating.Both Ce6 and TPLwere facilely co-loaded into the spherical supramolecular NPs(TPL+Ce6/NPs)by one-step nanoprecipitation method,with an ideal particle size(156.0 nm),acid pH-responsive drug release profile,and enhanced cellular internalization capacity.In view of the combination benefit of photodynamic therapy and chemotherapy,as well as co-encapsulation in the fabricated pH-sensitive supramolecular NPs,TPL+Ce6/NPs exhibited significant efficacy to suppress cellular proliferation,boost ROS level,lower MMP,and promote cellular apoptosis in vitro.Particularly,fluorescence imaging revealed that TPL+Ce6/NPs preferentially accumulated in the tumor tissue area,with higher intensity than that of free Ce6.As expected,upon 650-nm laser irradiation,TPL+Ce6/NPs exhibited a cascade of amplified synergistic chemo-photodynamic therapeutic benefits to suppress tumor progression in both hepatoma H22 tumor-bearingmice and B16 tumor-bearingmice.More importantly,lower systemic toxicitywas found in the tumor-bearingmice treated with TPL+Ce6/NPs.Overall,the designed supramolecular TPL+Ce6/NPs provided a promising alternative approach for chemo-photodynamic therapy in tumor treatment.展开更多
pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments ...pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.展开更多
A novel pH-sensitive nanoparticle drug delivery system (DDS) derived fl om natural polysaccharide pullulan for doxorubicin (DOX) release was prepared.Pullulan was functionalized by successive carboxymethylization and ...A novel pH-sensitive nanoparticle drug delivery system (DDS) derived fl om natural polysaccharide pullulan for doxorubicin (DOX) release was prepared.Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups.DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate.This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX.Trans...展开更多
A pH-sensitive modified polyacrylamide hydrogel was prepared by two steps and the modified polyacrylamide was characterized by ^1HNMR spectrum. The surface morphology and swelling behavior of the hydrogels were invest...A pH-sensitive modified polyacrylamide hydrogel was prepared by two steps and the modified polyacrylamide was characterized by ^1HNMR spectrum. The surface morphology and swelling behavior of the hydrogels were investigated.展开更多
A novel degradable pH-sensitive hydrogel with pendent carboxyl groups was designed and synthesized from ethylenediaminetetraacetic dianhydride （EDTAh） and butanediamine （BDA） with dicyclohexylcarbodiimide （DCC） ...A novel degradable pH-sensitive hydrogel with pendent carboxyl groups was designed and synthesized from ethylenediaminetetraacetic dianhydride （EDTAh） and butanediamine （BDA） with dicyclohexylcarbodiimide （DCC） as a condensating agent and BDA as a crosslinking agent. The obtained polymers were characterized by ^13C NMR, ^1H NMR and FTIR. The swelling experiments of the hydrogel in pH 3, 7, and 12 media indicated much higher swelling ratio in pH 12 media than in pH 3 and pH 7 media, exhibiting sound pH sensitivity. The pH sensitivity of this type of hydrogel may be regulated through controlling the type and the dose of the crosslinking agent.展开更多
With glucose as the template compound,a p H-sensitive hydrogel was prepared by polymerization of the modified glucose,acrylamide,and acrylic acid.The porous hydrogel showed the highest swelling ratio of 42.7 g/g at p ...With glucose as the template compound,a p H-sensitive hydrogel was prepared by polymerization of the modified glucose,acrylamide,and acrylic acid.The porous hydrogel showed the highest swelling ratio of 42.7 g/g at p H=7.4 and the best adsorption of methylene blue at p H=7.The Langmuir isotherm fitted very well to the equilibrium adsorption data with the maximum adsorption capacity of 49.1 mg/g.The adsorption kinetics were well described by the pseudo 2^(nd) order model.Adsorption studies suggested that the p H-sensitive glucose-based hydrogel could be used as an adsorbent for the removal of methylene blue from wastewater.Other applications of the hydrogel are on the way,such as scaffolding in the biomedical field and soil conditioning in agriculture.展开更多
Recently,multifunctional nanoparticles have shown great prospects in cancer treatment,which have the ability to simultaneously deliver the drug,image and target tumor cells.In this paper,we designed a luminescent nano...Recently,multifunctional nanoparticles have shown great prospects in cancer treatment,which have the ability to simultaneously deliver the drug,image and target tumor cells.In this paper,we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate(HA-FCNs/ACP)with multifunctional properties for drug delivery,bio-imaging,and targeting treatment.HA-FCNs/ACP shows an ability to load curcumin(Cur)with pH-sensitive responsive drug release behavior and excellent biocompatibility.HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells(A549 cells).Meanwhile,the viability of A549 cells was significantly inhibited in vitro.The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells.Hence,the as-prepared nanoparticles have promising applications in treating tumor disease.展开更多
Dendritic poly(amidoamine)-b-poly(L-glutamate)(PAMAM-b-PLG) biohybrids were synthesized by the ring-opening polymerization ofγ-benzyl-L-glutamate N-carboxyanhydride monomer,followed by the deprotection of benzyl grou...Dendritic poly(amidoamine)-b-poly(L-glutamate)(PAMAM-b-PLG) biohybrids were synthesized by the ring-opening polymerization ofγ-benzyl-L-glutamate N-carboxyanhydride monomer,followed by the deprotection of benzyl groups on poly(benzyl-L-glutamate),and were characterized by ~1H-NMR,FT-IR and gel permeation chromatography.The self-assembly behavior of the PAMAM-b-PLG biohybrid was investigated by means of UV-Vis,dynamic light scattering (DLS),transmission electronic microscopy(TEM) and ~1H-NMR.UV-Vis analysis ...展开更多
This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC...This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and ~1H-NMR. The buffering capacity of polyethylene glycol-distearoyl phosphatidylethanolamine(PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel(DOC) liposomes(TPOS-DOC-L) had a slower drugrelease rate at pH 7.4 similar to PEGylated-DOC liposomes(PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes(TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4( P < 0.01). Conversely, for PEGylated C6 liposomes(PEG-C6-L) and conventional C6 liposomes(C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes(DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-Lsignificantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.展开更多
The pH-sensitive copolymer hydrogels were prepared with the monomers of acrylic acid and N-vinyl-2-pyrrolidone based on gamma radiation technique. The morphology of the hydrogels was monitored by using scanning electr...The pH-sensitive copolymer hydrogels were prepared with the monomers of acrylic acid and N-vinyl-2-pyrrolidone based on gamma radiation technique. The morphology of the hydrogels was monitored by using scanning electron microscope. The influence of absorbed dose, monomer composition and concentration on the swelling ratio (SR) of the hydrogels were investigated in detail. The effect of pH and temperature of the swelling medium on the swelling behavior of the hydrogels were also examined. The results show that the SR of the copolymer hydrogels decreases with the monomer concentration and absorbed dose increasing. The copolymer hydrogels show a better pH-sensitive behavior. In alkaline solution, the SR of the hydrogels is much higher than in acid solution.展开更多
In this article, we synthesize of a novel starch-based superabsorbent hydrogel via graft copolymerization of mixtures of acrylic acid (AA) and 2-Hydroxy ethyl methacrylate (HEMA) onto starch backbones. The polymerizat...In this article, we synthesize of a novel starch-based superabsorbent hydrogel via graft copolymerization of mixtures of acrylic acid (AA) and 2-Hydroxy ethyl methacrylate (HEMA) onto starch backbones. The polymerization reaction was carried out in an aqueous medium and in the presence of ammonium persulfate (APS) as an initiator and N,N’-methylene bisacrylamide (MBA) as a crosslinker. The hydrogel structures were confirmed by FTIR spectroscopy. Furthermore, the swelling of superabsorbing hydrogels was examined in solutions with pH values ranging between 1 and 13. It showed a reversible pH-responsive behavior at pHs 2 and 8. This on-off switching behavior makes the synthesized hydrogels as an excellent candidate for controlled delivery of bioactive agents. A proposed mechanism for hydrogel formation was suggested and the structure of the product was established using FTIR and SEM spectroscopies.展开更多
By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a s...By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a spacer of five bonds. The structure and purity, molecular weight, hydrodynamic and thermosensitive properties of the obtained sample were studied by1H-and13C-NMR, FTIR spectroscopy, acid-base titration, light scattering, turbidimetry and viscometry. The observed ability of the imidazole-containing polymer to form and destroy associates in water-salt solutions at pH 6.6-7.4 and temperatures of 29-48℃ indicates that these are promising candidates for designing complex biomedical systems. The new polymer is able to form complexes with oligo-DNA more actively than poly(1-vinylimidazole), which is of interest for gene delivery applications. The polymer cross-linked with epichlorohydrin gives micro-relief coatings on the plastic surface, and the modified surface is able to attach negatively charged objects. This thermo-and pH-sensitive polymer modification can be applied to create finely controlled surfaces for cell culturing.展开更多
Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.D...Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes(Dexa-GP/ES/Pu NCs)have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota,and an underneath galactosylated-PLGA core(GP).The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C(MGL-2)surface receptor.Therefore,both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake.Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs.The nanocargoes were tested using in vitro,ex vivo techniques and dextran sodium sulfate(DSS)induced UC model.Prepared nanocargoes had desired physicochemical properties,drug release,cell uptake and cellular viability.Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2,and restoration of clinical,histopathological,biochemical indices,antioxidant balance,microbial alterations,FTIR spectra,and epithelial junctions’integrity.Thus,Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.展开更多
Albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting capacity.At present,only a few products,such as ABRAXANE®and FYARRO™...Albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting capacity.At present,only a few products,such as ABRAXANE®and FYARRO™,have been approved for clinical applications.The poor affinity of doxorubicin(DOX)for albumin,coupled with its numerous severe adverse reactions,poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX.In this study,we developed prodrugs by conjugating fatty acids of varying lengths with DOX.Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules.We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs.Compared to free DOX,all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm.Additionally,DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells.Significantly,the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids,impacting their in vivo pharmacokinetics,antitumor effectiveness and tumor accumulation.This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs,and it builds a good platform for creating ANPs which prioritize high drug loading,high efficiency,and minimal side effects.展开更多
To improve drug utilization,reduce the drug administration frequency,increase the release time,and reduce the drug side effects in the human body,we prepared(KHA/CMC-Fe^(3+))@CS hydrogel spheres using green and natura...To improve drug utilization,reduce the drug administration frequency,increase the release time,and reduce the drug side effects in the human body,we prepared(KHA/CMC-Fe^(3+))@CS hydrogel spheres using green and natural potassium humate(KHA),carboxymethyl cellulose(CMC),and chitosan(CS)as raw materials and Fe3+as a crosslinking agent,and loaded them with riboflavin for drug sustainedrelease study using the drop ball method.The tests with FTIR,SEM,TG,and X-ray diffractometer showed that the coordination among KHA,CMC,and Fe^(3+)formed a three-dimensional network structure,where cs was encapsulated on the surface of the hydrogel spheres via noncovalent bonding,resulting in good thermal stability.The stability,drug loading,swelling,and in vitro release of the(KHA/CMC-Fe^(3+))@CS hydrogel spheres were investigated.The results showed that the hydrogel spheres were significantly pH-sensitive,with 11.16 g/g higher swelling in an alkaline environment(pH=7.4)than that in an acidic environment(pH=1.2).The swelling and drug release process of the hydrogel spheres were analyzed using mathematical models,concluding that the hydrogel swelling follows Schott second-order swelling kinetics,and the drug release mechanism was Fickian delivery mode.展开更多
基金National Undergraduate Training Program for Innovation and Entrepreneurship of China (Grant No.202210288027).
文摘The abuse of plastic food packaging has brought about severe white pollution issues around the world.Developing green and sustainable biomass packaging is an effective way to solve this problem.Hence,a chitosan/sodium alginate-based multilayer film is fabricated via a layer-by-layer(LBL)self-assembly method.With the help of superior interaction between the layers,the multilayer film possesses excellent mechanical properties(with a tensile strength of 50 MPa).Besides,the film displays outstanding water retention property(blocking moisture of 97.56%)and ultraviolet blocking property.Anthocyanin is introduced into the film to detect the food quality since it is one natural plant polyphenol that is sensitive to the pH changes ranging from 1 to 13 in food when spoilage occurs.It is noted that the film is also bacteriostatic which is desired for food packaging.This study describes a simple technique for the development of advanced multifunctional and fully biodegradable food packaging film and it is a sustainable alternative to plastic packaging.
基金supported by the National Natural Science Foundation of China (51922111)the Science and Technology Development Fund, Macao SAR (File no. 0124/2019/A3)+1 种基金the University of Macao (File no. MYRG2022-00203-ICMS)Guangdong-Hong Kong-Macao Joint Laboratory of Optoelectronic and Magnetic Functional Materials (2019B121205002)
文摘Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.
基金Funded by the National Natural Science Foundation of China (No.50673077)National Basic Research Program of China (No.2006CB708602)
文摘Positively charged composite nanofiltration （NF） membranes were prepared through interfacial polymerization of poly[2-（N,N-dimethyl amino）ethyl methacrylate]（PDMAEMA） on porous polysulfone （PSF） substrate membranes. The effects of pH on swelling ratio （SR） of the pure crosslinked PDMAEMA membrane and on separation performances of the composite NF membrane were investigated. The results show that the quaternized amino groups produced through interfacial polymerization technique are soluble in both phases, which accelerate the crosslinking reaction as self-catalysts. The swelling/contracting behavior of the pure crosslinked PDMAEMA exhibited a well reversible pH sensitive property. Importantly, the rejection and flux of the composite NF membrane show pH-sensitive behavior in NF process. Furthermore, with the help of a relatively novel method to measure membrane conduction, the true zeta potentials calculated on the basis of the streaming potential measurements proved the pH-sensitive behavior of the NF membrane.
基金Funded by the National Natural Science Foundation of China (No.50673104)MOE, P R China
文摘A novel pH-sensitive complex was prepared by using oxidized konjac glucomannan and 4-aminosalicylic acid （4-ASA） through glutaraldehyde as a cross-linking agent. The product was characterized by FTIR and 13C NMR spectra, and the thermogravimetric analysis was also studied. The drug release studies in vitro showed that the amount of 4-ASA released from the complex was about 4%, 56% and 17% after 12 h at pH 1.2, 6.8 and 7.4, respectively. The data demonstrate that the rate of the drug release of the complex can be more effectively controlled by pH value. The results showed that the novel pH-sensitive complex could be potentially useful for colon-targeting drug delivery system.
基金This work was financially supported from the National Nature Science Foundation of China(NO.81360483)from the Nature Science Foundation of Ningxia(No.NZ12193).
文摘Most of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy.Based on physiological differences between the normal tissue and the tumor tissue,one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery systems.The copolymers with reversible protonationedeprotonation core units or acid-liable bonds between the therapeutic agents and the micelle-forming copolymers can be used to form pH-sensitive polymeric micelles for extracellular and intracellular drug smart release.These systems can be triggered to release drug in response to the slightly acidic extracellular fluids of tumor tissue after accumulation in tumor tissues via the enhanced permeability and retention effect,or they can be triggered to release drug in endosomes or lysosomes by pH-controlled micelle hydrolysis or dissociation after uptake by cells via the endocytic pathway.The pH-sensitive micelles have been proved the specific tumor cell targeting,enhanced cellular internalization,rapid drug release,and multidrug resistance reversal.The multifunctional polymeric micelles combining extracellular pH-sensitivity with receptor-mediated active targeting strategies are of great interest for enhanced tumor targeting.The micelles with receptor-mediated and intracellular pH targeting functions are internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells,which reverses multidrug resistance.The pH sensitivity strategy of the polymeric micelles facilitates the specific drug delivery with reduced systemic side effects and improved chemotherapeutical efficacy,and is a novel promising platform for tumor-targeting drug delivery.
基金supported by National Natural Science Foundation of China (No.81973662)Distinguished Young Scholar of Sichuan Provincial Science and Technology Department (No.2019JDJQ0049)111 Project (No.B18035)
文摘The combination of Ce6,an acknowledged photosensitizer,and TPL,a natural anticancer agent,has been demonstrated as a useful strategy to reinforce the tumor growth suppression,as well as decrease the systemic side effects compared with their monotherapy.However,in view of the optimal chemo-photodynamic combination efficiency,there is still short of the feasible nanovehicle to steadily co-deliver Ce6 and TPL,and stimuli-responsively burst release drugs in tumor site.Herein,we described the synergistic antitumor performance of a pH-sensitive supramolecular nanosystem,mediated by the host–guest complexing betweenβ-CD and acid pH-responsive amphiphilic co-polymer mPEG-PBAE-mPEG,showing the shell–core structural micelles with the tightβ-CD layer coating.Both Ce6 and TPLwere facilely co-loaded into the spherical supramolecular NPs(TPL+Ce6/NPs)by one-step nanoprecipitation method,with an ideal particle size(156.0 nm),acid pH-responsive drug release profile,and enhanced cellular internalization capacity.In view of the combination benefit of photodynamic therapy and chemotherapy,as well as co-encapsulation in the fabricated pH-sensitive supramolecular NPs,TPL+Ce6/NPs exhibited significant efficacy to suppress cellular proliferation,boost ROS level,lower MMP,and promote cellular apoptosis in vitro.Particularly,fluorescence imaging revealed that TPL+Ce6/NPs preferentially accumulated in the tumor tissue area,with higher intensity than that of free Ce6.As expected,upon 650-nm laser irradiation,TPL+Ce6/NPs exhibited a cascade of amplified synergistic chemo-photodynamic therapeutic benefits to suppress tumor progression in both hepatoma H22 tumor-bearingmice and B16 tumor-bearingmice.More importantly,lower systemic toxicitywas found in the tumor-bearingmice treated with TPL+Ce6/NPs.Overall,the designed supramolecular TPL+Ce6/NPs provided a promising alternative approach for chemo-photodynamic therapy in tumor treatment.
文摘pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.
基金the National Basic Research program of China (No.2005CB623903).
文摘A novel pH-sensitive nanoparticle drug delivery system (DDS) derived fl om natural polysaccharide pullulan for doxorubicin (DOX) release was prepared.Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups.DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate.This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX.Trans...
文摘A pH-sensitive modified polyacrylamide hydrogel was prepared by two steps and the modified polyacrylamide was characterized by ^1HNMR spectrum. The surface morphology and swelling behavior of the hydrogels were investigated.
基金supported by Natural Science Foundation of Chongqing (No.CSTC2006BB5010)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry (No.2007-1108).
文摘A novel degradable pH-sensitive hydrogel with pendent carboxyl groups was designed and synthesized from ethylenediaminetetraacetic dianhydride （EDTAh） and butanediamine （BDA） with dicyclohexylcarbodiimide （DCC） as a condensating agent and BDA as a crosslinking agent. The obtained polymers were characterized by ^13C NMR, ^1H NMR and FTIR. The swelling experiments of the hydrogel in pH 3, 7, and 12 media indicated much higher swelling ratio in pH 12 media than in pH 3 and pH 7 media, exhibiting sound pH sensitivity. The pH sensitivity of this type of hydrogel may be regulated through controlling the type and the dose of the crosslinking agent.
基金supported by the Research Grant of Jiangsu Province Biomass Energy and Materials Laboratory (JSBEM-S-201510)the Natural Science Foundation of Jiangsu Province of China (BK20160151)
文摘With glucose as the template compound,a p H-sensitive hydrogel was prepared by polymerization of the modified glucose,acrylamide,and acrylic acid.The porous hydrogel showed the highest swelling ratio of 42.7 g/g at p H=7.4 and the best adsorption of methylene blue at p H=7.The Langmuir isotherm fitted very well to the equilibrium adsorption data with the maximum adsorption capacity of 49.1 mg/g.The adsorption kinetics were well described by the pseudo 2^(nd) order model.Adsorption studies suggested that the p H-sensitive glucose-based hydrogel could be used as an adsorbent for the removal of methylene blue from wastewater.Other applications of the hydrogel are on the way,such as scaffolding in the biomedical field and soil conditioning in agriculture.
基金financially supported by the National Natural Science Foundation of China (31700689)Natural Science Foundation of Shanxi Province (201901D111115)+1 种基金Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (172040098-S)Transformation of Scientific and Technological Achievements Programs of Higher Education Institutions in Shanxi (2020CG015)
文摘Recently,multifunctional nanoparticles have shown great prospects in cancer treatment,which have the ability to simultaneously deliver the drug,image and target tumor cells.In this paper,we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate(HA-FCNs/ACP)with multifunctional properties for drug delivery,bio-imaging,and targeting treatment.HA-FCNs/ACP shows an ability to load curcumin(Cur)with pH-sensitive responsive drug release behavior and excellent biocompatibility.HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells(A549 cells).Meanwhile,the viability of A549 cells was significantly inhibited in vitro.The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells.Hence,the as-prepared nanoparticles have promising applications in treating tumor disease.
基金supported by the National Natural Science Foundation of China(No.20674050)Shanghai Leading Academic Discipline Project(No.B202)
文摘Dendritic poly(amidoamine)-b-poly(L-glutamate)(PAMAM-b-PLG) biohybrids were synthesized by the ring-opening polymerization ofγ-benzyl-L-glutamate N-carboxyanhydride monomer,followed by the deprotection of benzyl groups on poly(benzyl-L-glutamate),and were characterized by ~1H-NMR,FT-IR and gel permeation chromatography.The self-assembly behavior of the PAMAM-b-PLG biohybrid was investigated by means of UV-Vis,dynamic light scattering (DLS),transmission electronic microscopy(TEM) and ~1H-NMR.UV-Vis analysis ...
基金supported by National Natural Science Foundation of China (81102394)Natural Science Foundation of Liaoning Province (20170540575)
文摘This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and ~1H-NMR. The buffering capacity of polyethylene glycol-distearoyl phosphatidylethanolamine(PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel(DOC) liposomes(TPOS-DOC-L) had a slower drugrelease rate at pH 7.4 similar to PEGylated-DOC liposomes(PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes(TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4( P < 0.01). Conversely, for PEGylated C6 liposomes(PEG-C6-L) and conventional C6 liposomes(C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes(DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-Lsignificantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.
基金Natural Science Foundation of Henan Province (0611023900)
文摘The pH-sensitive copolymer hydrogels were prepared with the monomers of acrylic acid and N-vinyl-2-pyrrolidone based on gamma radiation technique. The morphology of the hydrogels was monitored by using scanning electron microscope. The influence of absorbed dose, monomer composition and concentration on the swelling ratio (SR) of the hydrogels were investigated in detail. The effect of pH and temperature of the swelling medium on the swelling behavior of the hydrogels were also examined. The results show that the SR of the copolymer hydrogels decreases with the monomer concentration and absorbed dose increasing. The copolymer hydrogels show a better pH-sensitive behavior. In alkaline solution, the SR of the hydrogels is much higher than in acid solution.
文摘In this article, we synthesize of a novel starch-based superabsorbent hydrogel via graft copolymerization of mixtures of acrylic acid (AA) and 2-Hydroxy ethyl methacrylate (HEMA) onto starch backbones. The polymerization reaction was carried out in an aqueous medium and in the presence of ammonium persulfate (APS) as an initiator and N,N’-methylene bisacrylamide (MBA) as a crosslinker. The hydrogel structures were confirmed by FTIR spectroscopy. Furthermore, the swelling of superabsorbing hydrogels was examined in solutions with pH values ranging between 1 and 13. It showed a reversible pH-responsive behavior at pHs 2 and 8. This on-off switching behavior makes the synthesized hydrogels as an excellent candidate for controlled delivery of bioactive agents. A proposed mechanism for hydrogel formation was suggested and the structure of the product was established using FTIR and SEM spectroscopies.
基金supported by the Russian Science Foundation(No.22-24-00474).
文摘By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a spacer of five bonds. The structure and purity, molecular weight, hydrodynamic and thermosensitive properties of the obtained sample were studied by1H-and13C-NMR, FTIR spectroscopy, acid-base titration, light scattering, turbidimetry and viscometry. The observed ability of the imidazole-containing polymer to form and destroy associates in water-salt solutions at pH 6.6-7.4 and temperatures of 29-48℃ indicates that these are promising candidates for designing complex biomedical systems. The new polymer is able to form complexes with oligo-DNA more actively than poly(1-vinylimidazole), which is of interest for gene delivery applications. The polymer cross-linked with epichlorohydrin gives micro-relief coatings on the plastic surface, and the modified surface is able to attach negatively charged objects. This thermo-and pH-sensitive polymer modification can be applied to create finely controlled surfaces for cell culturing.
基金the Higher Education Commission of Pakistan for the provision of HEC Indigenous scholarship (PIN No. 315-12214-2BS3-132) for the research workthe provision of grant under HEC NRPU project No. 9272/Federal/NRPU/R&D/HEC/2017
文摘Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes(Dexa-GP/ES/Pu NCs)have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota,and an underneath galactosylated-PLGA core(GP).The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C(MGL-2)surface receptor.Therefore,both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake.Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs.The nanocargoes were tested using in vitro,ex vivo techniques and dextran sodium sulfate(DSS)induced UC model.Prepared nanocargoes had desired physicochemical properties,drug release,cell uptake and cellular viability.Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2,and restoration of clinical,histopathological,biochemical indices,antioxidant balance,microbial alterations,FTIR spectra,and epithelial junctions’integrity.Thus,Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.
基金the National Key R&D Program of China(No.2022YFE0111600)National Natural Science Foundation of China(Nos.82272151 and 82204318)。
文摘Albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting capacity.At present,only a few products,such as ABRAXANE®and FYARRO™,have been approved for clinical applications.The poor affinity of doxorubicin(DOX)for albumin,coupled with its numerous severe adverse reactions,poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX.In this study,we developed prodrugs by conjugating fatty acids of varying lengths with DOX.Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules.We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs.Compared to free DOX,all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm.Additionally,DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells.Significantly,the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids,impacting their in vivo pharmacokinetics,antitumor effectiveness and tumor accumulation.This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs,and it builds a good platform for creating ANPs which prioritize high drug loading,high efficiency,and minimal side effects.
基金supported by the National Natural Science Foundation of China(grant No.51803114)Shaanxi Province Key R&D Program(grant No.2022NY-195)+4 种基金Xi'an City Innovation Capability Strong Foundation Plan-Agricultural Technology R&D(grant No.21NYYF0025)Shaanxi Province Education Department Service Local Special Program Project(grant No.22jcO15)Shaanxi Province Key R&D Program(grant No.2020SF-411)Industry-University-Research Cooperation Project of Yulin Science and Technology Bureau(grant No.CXY-2020-086)National Key R&D Projects in 2021(grant No.2021YFC1808900).
文摘To improve drug utilization,reduce the drug administration frequency,increase the release time,and reduce the drug side effects in the human body,we prepared(KHA/CMC-Fe^(3+))@CS hydrogel spheres using green and natural potassium humate(KHA),carboxymethyl cellulose(CMC),and chitosan(CS)as raw materials and Fe3+as a crosslinking agent,and loaded them with riboflavin for drug sustainedrelease study using the drop ball method.The tests with FTIR,SEM,TG,and X-ray diffractometer showed that the coordination among KHA,CMC,and Fe^(3+)formed a three-dimensional network structure,where cs was encapsulated on the surface of the hydrogel spheres via noncovalent bonding,resulting in good thermal stability.The stability,drug loading,swelling,and in vitro release of the(KHA/CMC-Fe^(3+))@CS hydrogel spheres were investigated.The results showed that the hydrogel spheres were significantly pH-sensitive,with 11.16 g/g higher swelling in an alkaline environment(pH=7.4)than that in an acidic environment(pH=1.2).The swelling and drug release process of the hydrogel spheres were analyzed using mathematical models,concluding that the hydrogel swelling follows Schott second-order swelling kinetics,and the drug release mechanism was Fickian delivery mode.
