Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a t...Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a traditional Chinese medicine(TCM)chemical monomer,could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway.Mechanistically,RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells,and eventually lead to ferroptosis.Furthermore,RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).To improve the delivery efficiency of RSV,a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol)(PCL-PEG)nanoparticles with erythrocyte membrane(RSV-NPs@RBCm).The RSV-NPs@RBCm provide the possibility to escape macrophage phagocytosis and have a long circulation effect.In addition,when coupled with a tumor-penetrating peptide iRGD,which could trigger enhanced tissue penetration tumor-specifically,the delivery of RSV-NPs@RBCm into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC.Altogether,our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform,it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.展开更多
As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of ...As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.展开更多
基金by the National Natural Science Foundation of China(81773211,81871942,82073308,81672411)the High-level startup fund of Nanjing Medical University(KY109RC2019010)the Natural Science Foundation of Jiangsu Province(BK20201086).
文摘Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a traditional Chinese medicine(TCM)chemical monomer,could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway.Mechanistically,RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells,and eventually lead to ferroptosis.Furthermore,RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).To improve the delivery efficiency of RSV,a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol)(PCL-PEG)nanoparticles with erythrocyte membrane(RSV-NPs@RBCm).The RSV-NPs@RBCm provide the possibility to escape macrophage phagocytosis and have a long circulation effect.In addition,when coupled with a tumor-penetrating peptide iRGD,which could trigger enhanced tissue penetration tumor-specifically,the delivery of RSV-NPs@RBCm into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC.Altogether,our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform,it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.
基金the National Natural Science Foundation of China(No.82073308 and No.81773211)the High-level startup fund of Nanjing Medical University(No.KY109RC2019010).
文摘As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.