Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics...Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics is highly advocated.Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention(EPR)effect caused by the inflammation.However,the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release.Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs,ligandmodified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects.This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands.Finally,challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.展开更多
Andrographolide (AG) is the characteristic constituent of Andrographis paniculata, of the Acanthaceae family. This plant is a well-known Asian medicinal plant that is widely used in India, China, and Thailand. A monog...Andrographolide (AG) is the characteristic constituent of Andrographis paniculata, of the Acanthaceae family. This plant is a well-known Asian medicinal plant that is widely used in India, China, and Thailand. A monograph of Herba Andrographidis (Chuanxinlian) is included in the Chinese Pharmacopoeia, which reports that this decoction can “remove heat, counteract toxicity, and reduce swellings.” The numerous potential activities of AG range from anti-inflammatory to anti-diabetic action, from neuroprotection to antitumor activity, and from hepatoprotective to anti-obesity properties. However, AG has low bioavailability and poor water solubility, which can limit its distribution and accumulation in the body after administration. In addition, AG is not stable in gastrointestinal alkaline and acidic environments, and has been reported to have a very short half-life. Among the diverse strategies that have been adopted to increase AG water solubility and permeability, the technological approach is the most useful way to develop appropriate delivery systems. This review reports on published studies related to microparticles (MPs) and nanoparticles (NPs) loaded with AG. MPs based on polylactic-glycolic acid (PLGA), alginic acid, and glucan derivatives have been developed for parenteral oral and pulmonary administration, respectively. NPs include vesicles (both liposomes and niosomes);polymeric NPs (based on polyvinyl alcohol, polymerized phenylboronic acid, PLGA, human serum albumin, poly ethylcyanoacrylate, and polymeric micelles);solid lipid NPs;microemulsions and nanoemulsions;gold NPs;nanocrystals;and nanosuspensions. Improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.展开更多
Recent development in nanotechnology has provided new tools for cancer therapy and diagnostics.Because of their small size,nanoscale devices readily interact with biomolecules both on the cell surface and inside the c...Recent development in nanotechnology has provided new tools for cancer therapy and diagnostics.Because of their small size,nanoscale devices readily interact with biomolecules both on the cell surface and inside the cell.Nanomaterials,such as fullerenes and their derivatives,are effective in terms of interactions with the immune system and have great potential as anticancer drugs.Comparatively,other nanomaterials are able to load active drugs to cancer cells by selectively using the unique tumor environment,such as their enhanced permeability,retention effect and the specific acidic microenvironment.Multifunctional and multiplexed nanoparticles,as the next generation of nanoparticles,are now being extensively investigated and are promising tools to achieve personalized and tailored cancer treatments.展开更多
Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,...Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.展开更多
Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated wit...Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.展开更多
A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles （GCNPs）, was developed for specific recognition and interaction with glucose transporters （Gluts） over-expressed by tumor cells. GC ...A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles （GCNPs）, was developed for specific recognition and interaction with glucose transporters （Gluts） over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan （CS）, and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of （187.9 ± 3.8） nm and a zeta potential of （-15.43 ± 0.31） mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin （DOX） could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-Ioaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline （pH 7.4）. In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.展开更多
Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investiga...Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptideconjugated active targeting liposomes(GE11-TLs)in SMMC7721 xenograft model.According to classification of individual cell types in high resolution images,biodistribution of macrophages,tumor cells,cells with high epidermal growth factor receptor(EGFR)expres sion and interstitial matrix in tumor microenvironment,in addition,their impacts on intra-tumor penetration of GE11-TLs were estimated.Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts.Tumor angiogenesis was of great heterogeneity from the periphery to the center region.However,the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs.We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drag delivery.展开更多
Objective To reduce the toxicity and side effects of arsenic trioxide(ATO)and provide a new approach for the treatment of primary liver cancer,a folic acid-modified calcium arsenite liposomal“target-controlled”drug ...Objective To reduce the toxicity and side effects of arsenic trioxide(ATO)and provide a new approach for the treatment of primary liver cancer,a folic acid-modified calcium arsenite liposomal“target-controlled”drug delivery system(FA-LP-CaAs)was fabricated using the reverse microemulsion method.Methods A Malvern particle size analyzer and a transmission electron microscope were employed to determine the particle size,distribution,zeta potential and morphology of FA-LP-CaAs.Further,inductively coupled plasma emission spectrometry was employed to determine the drug loading capacity,entrapment efficiency,and in vitro release behavior of FA-LP-CaAs.To determine its toxicity in human hepatoma cells(HepG2)and human normal hepatocytes(LO2)and its effect on HepG2 cell cycle and apoptosis,the MTT method was used.Laser confocal and flow cytometry were also employed to determine the uptake of FA-LP-CaAs by cells.After establishing a mouse liver cancer model,the in vivo distribution of the drug included in the formulation was investigated using in vivo fluorescence.To evaluate the liver cancer targeting and anti-tumor effects of FALP-CaAs in vivo,the distribution of ATO in tissues and changes in tumor volume and body weight after liposomal administration were investigated using hematoxylin-eosin(HE)-stained tumor sections.Results The particle size,zeta potential and PDI of FA-LP-CaAs were(122.67±2.18)nm,(12.81±0.75)mV and 0.22±0.01,respectively,while its drug loading capacity was 18.49%±1.14%.In vitro experimental results revealed that FA-LP-CaAs had a strong killing effect on HepG2 cells.Further,the cell uptake capacity of this formulation was found to improve.Based on in vivo assessments,FA-LP-CaAs could significantly increase the distribution of ATO in tumor sites and inhibit tumor growth.Conclusions Herein,an FA-LP-CaAs formulation was successfully fabricated.This liposomal drug delivery system had a round appearance,uniform particle size,good polydispersity coefficient,evident“core-shell”structure,high drug 展开更多
基金funded by the Science and Technology Development Fund,Macao S.A.R(Grant No.0023/2019/A and SKLQRCM(UM)-2020-2022,China)National Key Research and Development Program of China(Grant No.2017YFE0191500)the Research Fund of the University of Macao,Macao S.A.R.(Grant No.MYRG2019-00143-ICMS,China)
文摘Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics is highly advocated.Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention(EPR)effect caused by the inflammation.However,the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release.Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs,ligandmodified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects.This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands.Finally,challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.
基金the Fondazione Cassa Risparmio di Firenze for kindly supporting this review study
文摘Andrographolide (AG) is the characteristic constituent of Andrographis paniculata, of the Acanthaceae family. This plant is a well-known Asian medicinal plant that is widely used in India, China, and Thailand. A monograph of Herba Andrographidis (Chuanxinlian) is included in the Chinese Pharmacopoeia, which reports that this decoction can “remove heat, counteract toxicity, and reduce swellings.” The numerous potential activities of AG range from anti-inflammatory to anti-diabetic action, from neuroprotection to antitumor activity, and from hepatoprotective to anti-obesity properties. However, AG has low bioavailability and poor water solubility, which can limit its distribution and accumulation in the body after administration. In addition, AG is not stable in gastrointestinal alkaline and acidic environments, and has been reported to have a very short half-life. Among the diverse strategies that have been adopted to increase AG water solubility and permeability, the technological approach is the most useful way to develop appropriate delivery systems. This review reports on published studies related to microparticles (MPs) and nanoparticles (NPs) loaded with AG. MPs based on polylactic-glycolic acid (PLGA), alginic acid, and glucan derivatives have been developed for parenteral oral and pulmonary administration, respectively. NPs include vesicles (both liposomes and niosomes);polymeric NPs (based on polyvinyl alcohol, polymerized phenylboronic acid, PLGA, human serum albumin, poly ethylcyanoacrylate, and polymeric micelles);solid lipid NPs;microemulsions and nanoemulsions;gold NPs;nanocrystals;and nanosuspensions. Improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.
基金supported by the Ministry of Science and Technology of China (2011CB933401 & 2010CB934004)the National Natural Science Foundation of China (31070854)the Knowledge Innovation Program of the Chinese Academy of Sciences (KJCX2-YW-M02)
文摘Recent development in nanotechnology has provided new tools for cancer therapy and diagnostics.Because of their small size,nanoscale devices readily interact with biomolecules both on the cell surface and inside the cell.Nanomaterials,such as fullerenes and their derivatives,are effective in terms of interactions with the immune system and have great potential as anticancer drugs.Comparatively,other nanomaterials are able to load active drugs to cancer cells by selectively using the unique tumor environment,such as their enhanced permeability,retention effect and the specific acidic microenvironment.Multifunctional and multiplexed nanoparticles,as the next generation of nanoparticles,are now being extensively investigated and are promising tools to achieve personalized and tailored cancer treatments.
基金supported by the National Key Research and Development Plan(2018YFC2001500)National Natural Science Foundation of China(81972254,82172098).
文摘Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.
基金financial support provided by the National Natural Science Foundation of Shanghai(No.20ZR1420000)Shanghai Shen Kang Center Research Physician Training Program on Innovation and Translation Capabilities(No.SHDC2022CRS051)Three-Year Action Plan for Improving Clinical Research Capacity of International Peace Maternal and Child Health Hospital,Shanghai Jiao Tong University School of Medicine(No.IPMCH2022CR1-05).
文摘Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.
基金This research was supported by the National Natural Science Foundation of China （Grant Nos. 31000423 and 31301420） and the China Postdoctoral Science Foundation （Grant No. 2014M551965）.
文摘A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles （GCNPs）, was developed for specific recognition and interaction with glucose transporters （Gluts） over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan （CS）, and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of （187.9 ± 3.8） nm and a zeta potential of （-15.43 ± 0.31） mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin （DOX） could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-Ioaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline （pH 7.4）. In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.
基金supported by National Science Foundation of China(Grant Nos.30825045 and 81273465).
文摘Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptideconjugated active targeting liposomes(GE11-TLs)in SMMC7721 xenograft model.According to classification of individual cell types in high resolution images,biodistribution of macrophages,tumor cells,cells with high epidermal growth factor receptor(EGFR)expres sion and interstitial matrix in tumor microenvironment,in addition,their impacts on intra-tumor penetration of GE11-TLs were estimated.Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts.Tumor angiogenesis was of great heterogeneity from the periphery to the center region.However,the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs.We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drag delivery.
基金funding support from the National Natural Science Foundation of China (No. 81873014)。
文摘Objective To reduce the toxicity and side effects of arsenic trioxide(ATO)and provide a new approach for the treatment of primary liver cancer,a folic acid-modified calcium arsenite liposomal“target-controlled”drug delivery system(FA-LP-CaAs)was fabricated using the reverse microemulsion method.Methods A Malvern particle size analyzer and a transmission electron microscope were employed to determine the particle size,distribution,zeta potential and morphology of FA-LP-CaAs.Further,inductively coupled plasma emission spectrometry was employed to determine the drug loading capacity,entrapment efficiency,and in vitro release behavior of FA-LP-CaAs.To determine its toxicity in human hepatoma cells(HepG2)and human normal hepatocytes(LO2)and its effect on HepG2 cell cycle and apoptosis,the MTT method was used.Laser confocal and flow cytometry were also employed to determine the uptake of FA-LP-CaAs by cells.After establishing a mouse liver cancer model,the in vivo distribution of the drug included in the formulation was investigated using in vivo fluorescence.To evaluate the liver cancer targeting and anti-tumor effects of FALP-CaAs in vivo,the distribution of ATO in tissues and changes in tumor volume and body weight after liposomal administration were investigated using hematoxylin-eosin(HE)-stained tumor sections.Results The particle size,zeta potential and PDI of FA-LP-CaAs were(122.67±2.18)nm,(12.81±0.75)mV and 0.22±0.01,respectively,while its drug loading capacity was 18.49%±1.14%.In vitro experimental results revealed that FA-LP-CaAs had a strong killing effect on HepG2 cells.Further,the cell uptake capacity of this formulation was found to improve.Based on in vivo assessments,FA-LP-CaAs could significantly increase the distribution of ATO in tumor sites and inhibit tumor growth.Conclusions Herein,an FA-LP-CaAs formulation was successfully fabricated.This liposomal drug delivery system had a round appearance,uniform particle size,good polydispersity coefficient,evident“core-shell”structure,high drug
