Hepatocellular carcinoma(HCC)has become the fourth predominant cause of cancer-related deaths worldwide,and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surg...Hepatocellular carcinoma(HCC)has become the fourth predominant cause of cancer-related deaths worldwide,and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surgical treatment due to drug resista nce and great toxic effects.Triptolide(TP),a key ingredient from the traditional Chinese medical herb,has been utilized to treat inflammation and antitumor for centuries.However,investigations of this potent agent have been met with only limited success due to the severe systemic toxicities in patients and low water solubility as well as its high toxicity over the past two decades.Herein,we reported the development of a reduction-responsive drug delive ry system loaded with TP fo r glutathione(GSH)-trigge red drug release for cancer therapy.With the GSH-sensitive TP loaded nanoparticles,the remarkable increases in tumor accumulation and amelioration of drug toxicity in animals are demonstrated,which is likely due to sustained stepwise release of active TP within cancer cells.Moreover,in a patient-derived tumor xenograft model of liver cancer,administration of tritolide nanoparticles enhances the antitumor efficacy relative to administration of free TP.These findings indicate that GSH-sensitive release of TP may be a promising strategy for cancer treatment.展开更多
Celastrol,a Chinese herbal medicine,has exhibited anticancer activity in many types of cancer cells.However,the further clinical application of celastrol is restricted by its poor water solubility and serious side eff...Celastrol,a Chinese herbal medicine,has exhibited anticancer activity in many types of cancer cells.However,the further clinical application of celastrol is restricted by its poor water solubility and serious side effects.Furthermore,the apoptosis mechanism of tumor cells induced by celastrol has not been exhausted yet.In this study,we developed a reduction sensitive polymeric vector for tumor-targeted celastrol delivery.And our researches indicated that the celastrol could be delivered by reductionsensitive nanomedicine(RSNMs)with a controlled release strategy.Meanwhile,the cell uptake results indicated that excellent reduction-sensitive behavior of RSNMs could effectively accelerate celastrol into the human retinoblastoma(RB)cell.The cell cytotoxicity assay demonstrated that celastrol inhibited proliferation of human RB Y79 cells growth in a dose-dependent manner.Furthermore,the results of flow cytometry and terminal dUTP nick-end labeling(TUNEL)staining showed that celastrol induced apoptosis of the RB Y79 cells,and revealed a time-dependent increase in apoptosis induction of RB Y79 cells.The results of western blotting showed that celastrol induced the apoptosis of human RB Y79 cells involving the activation of caspase-3 and caspase-9.In conclusion,our results revealed that RSNMs may be utilized as a novel therapy for retinoblastoma.展开更多
Hyaluronic acid(HA)is a natural polysaccharide that has gained much attention due to its biocompatibility,enzyme degradation capacity and active tumor targeting capacity.Its receptor,CD44,is overexpressed in many kind...Hyaluronic acid(HA)is a natural polysaccharide that has gained much attention due to its biocompatibility,enzyme degradation capacity and active tumor targeting capacity.Its receptor,CD44,is overexpressed in many kinds of cancers and is associated with tumor progress,infiltration and metastasis.Therefore,many researchers have developed various HA-based drug delivery systems for CD44-mediated tumor targeting.In this review,we systemically overview the basic theory of HA,its receptor and hyaluronidase,then we categorize the studies in HA-based drug delivery systems according to the functions of HA,including tumor-targeting materials,enzyme-sensitive biodegradable modality,pHsensitive component,reduction-sensitive component,and the gel backbone.Finally,the perspective is discussed.展开更多
Cell-penetrating peptides(CPPs)have been widely used to enhance the membrane transloca-tion of various carriers for many years,but the non-specificity of CPPs seriously limits their utility in vivo.In this study,chole...Cell-penetrating peptides(CPPs)have been widely used to enhance the membrane transloca-tion of various carriers for many years,but the non-specificity of CPPs seriously limits their utility in vivo.In this study,cholesterol-anchored,reduction-sensitive PEG(first synthesized by our laboratory)was applied to develop a co-modified liposome with improved tumor targeting.Following optimization of the formulation,the in vitro and in vivo properties of the co-modified liposome were evaluated.The co-modified liposome had a much lower cellular uptake and tumor spheroid uptake,but a much higher tumor accumulation compared to CPP-modified liposome,indicating the non-specific penetration of CPPs could be attenuated by the outer PEG coating.With the addition of exogenous reducing agent,both the in vitro and in vivo cellular uptake was markedly increased,demonstrating that the reduction-sensitive PEG coating achieved a controllable detachment from the surface of liposomes and did not affect the penetrating abilities of CPPs.The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.展开更多
基金the National Natural Science Foundation of China(Nos.81572797,81701817)the Natural Science Foundation of Guangdong Province(No.2019A1515011619)+1 种基金Guangdong Provincial Science and Technology Department(No.2016A030311015)Shenzhen Science and Technology Project(No.JCYJ20180507183842516)。
文摘Hepatocellular carcinoma(HCC)has become the fourth predominant cause of cancer-related deaths worldwide,and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surgical treatment due to drug resista nce and great toxic effects.Triptolide(TP),a key ingredient from the traditional Chinese medical herb,has been utilized to treat inflammation and antitumor for centuries.However,investigations of this potent agent have been met with only limited success due to the severe systemic toxicities in patients and low water solubility as well as its high toxicity over the past two decades.Herein,we reported the development of a reduction-responsive drug delive ry system loaded with TP fo r glutathione(GSH)-trigge red drug release for cancer therapy.With the GSH-sensitive TP loaded nanoparticles,the remarkable increases in tumor accumulation and amelioration of drug toxicity in animals are demonstrated,which is likely due to sustained stepwise release of active TP within cancer cells.Moreover,in a patient-derived tumor xenograft model of liver cancer,administration of tritolide nanoparticles enhances the antitumor efficacy relative to administration of free TP.These findings indicate that GSH-sensitive release of TP may be a promising strategy for cancer treatment.
基金supported by the National Natural Science Foundation of China(Nos.81600775,U1904176 and 21504082)the Science and Technology Program of Henan Province,China(No.202102310072)the Medical Science and Technology Program of Henan Province,China(Nos.2018020398 and SB201902026)。
文摘Celastrol,a Chinese herbal medicine,has exhibited anticancer activity in many types of cancer cells.However,the further clinical application of celastrol is restricted by its poor water solubility and serious side effects.Furthermore,the apoptosis mechanism of tumor cells induced by celastrol has not been exhausted yet.In this study,we developed a reduction sensitive polymeric vector for tumor-targeted celastrol delivery.And our researches indicated that the celastrol could be delivered by reductionsensitive nanomedicine(RSNMs)with a controlled release strategy.Meanwhile,the cell uptake results indicated that excellent reduction-sensitive behavior of RSNMs could effectively accelerate celastrol into the human retinoblastoma(RB)cell.The cell cytotoxicity assay demonstrated that celastrol inhibited proliferation of human RB Y79 cells growth in a dose-dependent manner.Furthermore,the results of flow cytometry and terminal dUTP nick-end labeling(TUNEL)staining showed that celastrol induced apoptosis of the RB Y79 cells,and revealed a time-dependent increase in apoptosis induction of RB Y79 cells.The results of western blotting showed that celastrol induced the apoptosis of human RB Y79 cells involving the activation of caspase-3 and caspase-9.In conclusion,our results revealed that RSNMs may be utilized as a novel therapy for retinoblastoma.
基金supported by Doctoral Research Startup Fund of the Affiliated Hospital of Southwest Medical University,China(16250)National Natural Science Foundation of China(81872806 and 31571016)+1 种基金Young Elite Scientists Sponsorship Program by CAST,China(2017QNRC001)Luzhou Municipal Government-Southwest Medical University Science and Technology Strategic Cooperation Project,China(2018LZXNYPT02).
文摘Hyaluronic acid(HA)is a natural polysaccharide that has gained much attention due to its biocompatibility,enzyme degradation capacity and active tumor targeting capacity.Its receptor,CD44,is overexpressed in many kinds of cancers and is associated with tumor progress,infiltration and metastasis.Therefore,many researchers have developed various HA-based drug delivery systems for CD44-mediated tumor targeting.In this review,we systemically overview the basic theory of HA,its receptor and hyaluronidase,then we categorize the studies in HA-based drug delivery systems according to the functions of HA,including tumor-targeting materials,enzyme-sensitive biodegradable modality,pHsensitive component,reduction-sensitive component,and the gel backbone.Finally,the perspective is discussed.
基金The work was funded by the National Natural Science Foundation of China(81373337)the National Basic Research Program of China(973 Program,2013CB932504).
文摘Cell-penetrating peptides(CPPs)have been widely used to enhance the membrane transloca-tion of various carriers for many years,but the non-specificity of CPPs seriously limits their utility in vivo.In this study,cholesterol-anchored,reduction-sensitive PEG(first synthesized by our laboratory)was applied to develop a co-modified liposome with improved tumor targeting.Following optimization of the formulation,the in vitro and in vivo properties of the co-modified liposome were evaluated.The co-modified liposome had a much lower cellular uptake and tumor spheroid uptake,but a much higher tumor accumulation compared to CPP-modified liposome,indicating the non-specific penetration of CPPs could be attenuated by the outer PEG coating.With the addition of exogenous reducing agent,both the in vitro and in vivo cellular uptake was markedly increased,demonstrating that the reduction-sensitive PEG coating achieved a controllable detachment from the surface of liposomes and did not affect the penetrating abilities of CPPs.The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.
