Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells....Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.展开更多
This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nanoparticles, which was carried out in a rotating p...This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nanoparticles, which was carried out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxime Axetil (CFA) particles, 200–400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), and 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation and drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing and the ease of scaling-up.展开更多
Novel multifunctional nanoparticles containing a magnetic Fe3O4@SiO2 sphere and a biocompatible block copolymer poly(ethylene glycol)-b-poly(aspartate)(PEG-b-PAsp) were prepared.The silica coated on the superparamagne...Novel multifunctional nanoparticles containing a magnetic Fe3O4@SiO2 sphere and a biocompatible block copolymer poly(ethylene glycol)-b-poly(aspartate)(PEG-b-PAsp) were prepared.The silica coated on the superparamagnetic core was able to achieve a magnetic dispersivity,as well as to protect Fe3O4 against oxidation and acid corrosion.The PAsp block was grafted to the surface of Fe3O4@SiO2 nanoparticles by amido bonds,and the PEG block formed the outermost shell.The anticancer agent doxorubicin(DOX) was loaded into the hybrid nanoparticles via an electrostatic interaction between DOX and PAsp.The release rate of DOX could be adjusted by the pH value.展开更多
Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells(MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. H...Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells(MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles(NP)with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel(DTX) in NP, delivered via MSC accumulated in the lung. Both in vitro MSC/A549 cell experiments and in vivo MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. In vivo assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.展开更多
Hypoxia is a serious impediment to current treatments of many malignant tumors.Catalase,an antioxidant enzyme,is capable of decomposing endogenous hydrogen peroxide(H2O2)into oxygen for tumor reoxygenation,but suffere...Hypoxia is a serious impediment to current treatments of many malignant tumors.Catalase,an antioxidant enzyme,is capable of decomposing endogenous hydrogen peroxide(H2O2)into oxygen for tumor reoxygenation,but suffered from in vivo instability and limited delivery to deep interior hypoxic regions in tumor.Herein,a deep-penetrated nanocatalase-loading DiIC18(5,DiD)and soravtansine(Cat@PDS)were provided by coating catalase nanoparticles with PEGylated phospholipids membrane,stimulating the structure and function of erythrocytes to relieve tumor hypoxia for enhanced chemophotodynamic therapy.After intravenous administration,Cat@PDS preferentially accumulated at tumor sites,flexibly penetrated into the interior regions of tumor mass and remarkably relieved the hypoxic status in tumor.Notably,the Cat@PDS+laser treatment produced striking inhibition of tumor growth and resulted in a 97.2%suppression of lung metastasis.Thus,the phospholipids membrane-coated nanocatalase system represents an encouraging nanoplatform to relieve tumor hypoxia and synergize the chemophotodynamic cancer therapy.展开更多
The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tu...The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.展开更多
Because of their high efficiency, antibiotics have long been the primary treatment for infections, but the rise of drug-resistant pathogens has become a therapeutic concern. Nanoparticles, as novel biomaterials, are c...Because of their high efficiency, antibiotics have long been the primary treatment for infections, but the rise of drug-resistant pathogens has become a therapeutic concern. Nanoparticles, as novel biomaterials, are currently gaining global attention to combat them. Drug-resistant diseases may need the use of nanoparticles as a viable therapeutic option. By altering target locations and enzymes, decreasing cell permeability, inactivating enzymes, and increasing efflux by overexpressing efflux pumps, they can bypass conventional resistance mechanisms. Therefore, understanding how metal and metal oxide nanoparticles affect microorganisms that are resistant to antimicrobial drugs is the main objective of this review. Accordingly, the uses of metal and metal oxide nanoparticles in the fight against drug-resistant diseases appear promising. However, their mechanism of action, dose, and possible long-term effects require special attention and future research. Furthermore, repeated use of silver nanoparticles may cause gram-negative microorganisms to acquire resistance, necessitating additional study.展开更多
Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging cells.Immune cell dysfunction can cause an inability to recognize,react,and remo...Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging cells.Immune cell dysfunction can cause an inability to recognize,react,and remove these hazards,resulting in cancers,inflammatory diseases,autoimmune diseases,and infections.Immune cells regulation has shown great promise in treating disease,and immune agonists are usually used to treat cancers and infections caused by immune suppression.In contrast,immunosuppressants are used to treat inflammatory and autoimmune diseases.However,the key to maintaining health is to restore balance to the immune system,as excessive activation or inhibition of immune cells is a common complication of immunotherapy.Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors,nucleic acid,and proteins.Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function.In this review,we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.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
Drug resistance presents one of the major causes for the failure of cancer chemotherapy.Cancer stem-like cells(CSCs),a population of self-renewal cells with high tumorigenicity and innate chemoresistance,can survive c...Drug resistance presents one of the major causes for the failure of cancer chemotherapy.Cancer stem-like cells(CSCs),a population of self-renewal cells with high tumorigenicity and innate chemoresistance,can survive conventional chemotherapy and generate increased resistance.Here,we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent,all-trans retinoic acid and the chemotherapeutic drug,doxorubicin to overcome the CSC-associated chemoresistance.The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation.In the hypoxic CSCs,ATRA is released to induce differentiation of the CSCs,and in the differentiating CSCs with decreased chemoresistance,DOX is released upon elevation of reactive oxygen species to cause subsequent cell death.In the bulk tumor cells,the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect.This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism.We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.展开更多
Tumor necrosis factor receptors(TNFRs)are promising targets for cancer therapy.However,activating their downstream signaling requires cross-linking of TNFRs.Herein,to devise strong agonists of TNFRs,ligands targeting ...Tumor necrosis factor receptors(TNFRs)are promising targets for cancer therapy.However,activating their downstream signaling requires cross-linking of TNFRs.Herein,to devise strong agonists of TNFRs,ligands targeting TNFRs,such as OX40L and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),were fused with a multivalent protein scaffold(MV)to prepare multivalent agonists for cross-linking TNFRs.The nano-clustered multivalent-OX40L(MV-OX40L)and MV-TRAIL could promote T cell activation and directly induce tumor cell apoptosis.Moreover,to develop a universal nano-adaptor for the rapid preparation of multivalent agonists of different TNFRs,the Fc receptor that could immobilize antibodies was fused with MV to prepare MV-FcR,which could multimerize commercial agonist antibodies targeting TNFRs,such as anti-OX40 antibody(αOX40).Simply incubatingαOX40 with MV-FcR could prepare MV-αOX40 to enhance its antitumor efficacy.In addition,MV-FcR could multimerize with other therapeutic antibodies,such as anti-PD-L1 antibody,to enhance their valency.This study provides a promising strategy for engineering multivalent antitumor protein drugs.展开更多
Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising...Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising intrinsic capability of recovering itself after injury.However,the hostile extrinsic microenvironment significantly hinders axon regeneration.Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration.Particularly,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries.In this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury.Importantly,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination.To specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology.We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.展开更多
Silica nanoparticles （SiNPs） have been widely engineered for biomedical applications, such as bioimaging and drug delivery, because of their high tunability, which allows them to perform specific functions. In this ...Silica nanoparticles （SiNPs） have been widely engineered for biomedical applications, such as bioimaging and drug delivery, because of their high tunability, which allows them to perform specific functions. In this review, we discuss the functionalization and performance of SiNPs for nucleic acid delivery. Nucleic acids, including plasmid DNA （pDNA） and small interfering RNA （siRNA）, constitute the next generation molecular drugs for the treatment of intractable diseases. However, their low bioavailability requires delivery systems that can circumvent nuclease attack and kidney filtration to ensure efficient access to the target cell cytoplasm or nucleus. First, we discussed the biological significance of nucleic acids and the parameters required for their successful delivery. Next, we reviewed SiNP designing for nucleic acid delivery with respect to nucleic acid loading and release, cellular uptake, endosomal escape, and biocompatibility. In addition, we discussed the co-delivery potential of SiNPs. Finally, we analyzed the current challenges and future directions of SiNPs for advanced nucleic acid delivery.展开更多
基金the financial support from National Natural Science Foundation of China (81773911, 81690263, 81673372, and 81361140344)National Basin Research Program of China (2013CB 932500)Development Project of Shanghai Peak Disciplines– Integrated Medicine (No. 20150407)
文摘Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.
基金"863 Plan" of China(grant no. 2001AA218061, no. 2004AA218042,and no.2006AA030202)the National Natural Science Foundation(NSF) of China (grant no. 20146002,no.20236020,and no.20325621)Nano Materials Technology Pte. Ltd., Singapore
文摘This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nanoparticles, which was carried out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxime Axetil (CFA) particles, 200–400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), and 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation and drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing and the ease of scaling-up.
基金supported by the National Natural Science Foundation of China (Grant Nos 20774051,50625310,and 50830103)the Opening Foundation of Sichuan University
文摘Novel multifunctional nanoparticles containing a magnetic Fe3O4@SiO2 sphere and a biocompatible block copolymer poly(ethylene glycol)-b-poly(aspartate)(PEG-b-PAsp) were prepared.The silica coated on the superparamagnetic core was able to achieve a magnetic dispersivity,as well as to protect Fe3O4 against oxidation and acid corrosion.The PAsp block was grafted to the surface of Fe3O4@SiO2 nanoparticles by amido bonds,and the PEG block formed the outermost shell.The anticancer agent doxorubicin(DOX) was loaded into the hybrid nanoparticles via an electrostatic interaction between DOX and PAsp.The release rate of DOX could be adjusted by the pH value.
基金supported by grants from the Natural Science Foundation of China(Nos.81771966,31371404,31401187 and 31571429)the Fundamental Research Funds for the Central Universities(Lin Mei,China)+4 种基金the Guangdong Natural Science Funds for Distinguished Young Scholar(No.2014A030306036,China)the Natural Science Foundation of Guangdong,China(2015A030311041,2015A030313763)Science and Technology Planning Project of Guangdong Province,China(Nos.2016A020217001 and 2014A020212466)the Shenzhen Science and Technology Innovation Committee(JCYJ20160301152300347,JCYJ20160531195129079,JCYJ20170412095722235,JCYJ2016042-9171931438,and GJHZ20150316160614842,China)Guangdong Province Medical Science and Technology Research Fund(A2016445,China)
文摘Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells(MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles(NP)with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel(DTX) in NP, delivered via MSC accumulated in the lung. Both in vitro MSC/A549 cell experiments and in vivo MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. In vivo assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.
基金financially supported by the Strategic Priority Research Program of CAS(XDA12050307,China)National Natural Science Foundation of China(31771092,81803444)Youth Innovation Promotion Association of CAS and FudanSIMM Joint Research Fund(FU-SIMM20182005,China)
文摘Hypoxia is a serious impediment to current treatments of many malignant tumors.Catalase,an antioxidant enzyme,is capable of decomposing endogenous hydrogen peroxide(H2O2)into oxygen for tumor reoxygenation,but suffered from in vivo instability and limited delivery to deep interior hypoxic regions in tumor.Herein,a deep-penetrated nanocatalase-loading DiIC18(5,DiD)and soravtansine(Cat@PDS)were provided by coating catalase nanoparticles with PEGylated phospholipids membrane,stimulating the structure and function of erythrocytes to relieve tumor hypoxia for enhanced chemophotodynamic therapy.After intravenous administration,Cat@PDS preferentially accumulated at tumor sites,flexibly penetrated into the interior regions of tumor mass and remarkably relieved the hypoxic status in tumor.Notably,the Cat@PDS+laser treatment produced striking inhibition of tumor growth and resulted in a 97.2%suppression of lung metastasis.Thus,the phospholipids membrane-coated nanocatalase system represents an encouraging nanoplatform to relieve tumor hypoxia and synergize the chemophotodynamic cancer therapy.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20110071130011)the National Science and Technology Major Project (No. 2012ZX09304004)
文摘The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.
文摘Because of their high efficiency, antibiotics have long been the primary treatment for infections, but the rise of drug-resistant pathogens has become a therapeutic concern. Nanoparticles, as novel biomaterials, are currently gaining global attention to combat them. Drug-resistant diseases may need the use of nanoparticles as a viable therapeutic option. By altering target locations and enzymes, decreasing cell permeability, inactivating enzymes, and increasing efflux by overexpressing efflux pumps, they can bypass conventional resistance mechanisms. Therefore, understanding how metal and metal oxide nanoparticles affect microorganisms that are resistant to antimicrobial drugs is the main objective of this review. Accordingly, the uses of metal and metal oxide nanoparticles in the fight against drug-resistant diseases appear promising. However, their mechanism of action, dose, and possible long-term effects require special attention and future research. Furthermore, repeated use of silver nanoparticles may cause gram-negative microorganisms to acquire resistance, necessitating additional study.
基金supported by the National Key R&D Program of China(2022YFB3808100)the National Natural Science Foundation of China(82072048,52130301,and 32271442)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2022B1515020025)the Science and Technology Program of Guangzhou,China(202103030004)the Fundamental Research Funds for the Central Universities(2022ZYGXZR102).
文摘Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging cells.Immune cell dysfunction can cause an inability to recognize,react,and remove these hazards,resulting in cancers,inflammatory diseases,autoimmune diseases,and infections.Immune cells regulation has shown great promise in treating disease,and immune agonists are usually used to treat cancers and infections caused by immune suppression.In contrast,immunosuppressants are used to treat inflammatory and autoimmune diseases.However,the key to maintaining health is to restore balance to the immune system,as excessive activation or inhibition of immune cells is a common complication of immunotherapy.Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors,nucleic acid,and proteins.Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function.In this review,we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.
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 the National Natural Science Foundation of China(82273876,81971730,81673381,82104090)the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China(171028)+2 种基金the Project of State Key Laboratory of Natural Medicines of China Pharmaceutical University(SKLNMZZ202024,China)the Natural Science Foundation of Jiangsu Province(BK20210425,China)the Postdoctoral Research Funding of Jiangsu Province(2021K051A,China).
文摘Drug resistance presents one of the major causes for the failure of cancer chemotherapy.Cancer stem-like cells(CSCs),a population of self-renewal cells with high tumorigenicity and innate chemoresistance,can survive conventional chemotherapy and generate increased resistance.Here,we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent,all-trans retinoic acid and the chemotherapeutic drug,doxorubicin to overcome the CSC-associated chemoresistance.The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation.In the hypoxic CSCs,ATRA is released to induce differentiation of the CSCs,and in the differentiating CSCs with decreased chemoresistance,DOX is released upon elevation of reactive oxygen species to cause subsequent cell death.In the bulk tumor cells,the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect.This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism.We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.
基金National Key R&D Program of China,Grant/Award Number:2022YFB3808100National Natural Science Foundation of China,Grant/Award Numbers:32271442,52130301,82072048+2 种基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2022B1515020025Science and Technology Program of Guangzhou,China,Grant/Award Number:202103030004Fundamental Research Funds for the Central Universities,Grant/Award Number:2022ZYGXZR102。
文摘Tumor necrosis factor receptors(TNFRs)are promising targets for cancer therapy.However,activating their downstream signaling requires cross-linking of TNFRs.Herein,to devise strong agonists of TNFRs,ligands targeting TNFRs,such as OX40L and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),were fused with a multivalent protein scaffold(MV)to prepare multivalent agonists for cross-linking TNFRs.The nano-clustered multivalent-OX40L(MV-OX40L)and MV-TRAIL could promote T cell activation and directly induce tumor cell apoptosis.Moreover,to develop a universal nano-adaptor for the rapid preparation of multivalent agonists of different TNFRs,the Fc receptor that could immobilize antibodies was fused with MV to prepare MV-FcR,which could multimerize commercial agonist antibodies targeting TNFRs,such as anti-OX40 antibody(αOX40).Simply incubatingαOX40 with MV-FcR could prepare MV-αOX40 to enhance its antitumor efficacy.In addition,MV-FcR could multimerize with other therapeutic antibodies,such as anti-PD-L1 antibody,to enhance their valency.This study provides a promising strategy for engineering multivalent antitumor protein drugs.
基金supported by the National Natural Science Foundation of China(No.81974210)the Science and Technology Planning Project of Guangdong Province,China(No.2020A0505100045)the Natural Science Foundation of Guangdong Province(No.2019A1515010671),all to CKT.
文摘Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising intrinsic capability of recovering itself after injury.However,the hostile extrinsic microenvironment significantly hinders axon regeneration.Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration.Particularly,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries.In this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury.Importantly,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination.To specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology.We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.
文摘Silica nanoparticles （SiNPs） have been widely engineered for biomedical applications, such as bioimaging and drug delivery, because of their high tunability, which allows them to perform specific functions. In this review, we discuss the functionalization and performance of SiNPs for nucleic acid delivery. Nucleic acids, including plasmid DNA （pDNA） and small interfering RNA （siRNA）, constitute the next generation molecular drugs for the treatment of intractable diseases. However, their low bioavailability requires delivery systems that can circumvent nuclease attack and kidney filtration to ensure efficient access to the target cell cytoplasm or nucleus. First, we discussed the biological significance of nucleic acids and the parameters required for their successful delivery. Next, we reviewed SiNP designing for nucleic acid delivery with respect to nucleic acid loading and release, cellular uptake, endosomal escape, and biocompatibility. In addition, we discussed the co-delivery potential of SiNPs. Finally, we analyzed the current challenges and future directions of SiNPs for advanced nucleic acid delivery.
