Nanocarriers have emerged as a promising cancer drug delivery strategy.Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemothe...Nanocarriers have emerged as a promising cancer drug delivery strategy.Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy.Vitamin E derivatives have many essential functions for drug delivery applications,such as biological components that are hydrophobic,stable,water-soluble enhancing compounds,and anticancer activity.In addition,vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins.Here,we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system(O-CMCTS-VES).The synthesized polymers were characterized by Fourier Transform IR,and 1H NMR spectra.The mean sizes of O-CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm.The drug loading contents were 6.1%,13.0%and 10.6%with the weight ratio of DOX to O-CMCTS-VES corresponding 1:10,2:10 and 3:10,and the corresponding EEs were 64.3%,74.5%and 39.7%.Cytotoxicity test,hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo.Drug release experiments implied good pH sensitivity and sustained-release effect.The DOX/O-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%.In the in vivo study by using H22 cells implanted Balb/C mice,DOX/O-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%.The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.展开更多
基金The authors wish to thank National Natural Science Foundation of China(No.51773188)Key Project of Natural Science Foundation of Shandong Province(No.ZR2020KE016)The National Key Research and Development Program of China(No.2018YFC1105602,2018YFD0900601).
文摘Nanocarriers have emerged as a promising cancer drug delivery strategy.Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy.Vitamin E derivatives have many essential functions for drug delivery applications,such as biological components that are hydrophobic,stable,water-soluble enhancing compounds,and anticancer activity.In addition,vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins.Here,we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system(O-CMCTS-VES).The synthesized polymers were characterized by Fourier Transform IR,and 1H NMR spectra.The mean sizes of O-CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm.The drug loading contents were 6.1%,13.0%and 10.6%with the weight ratio of DOX to O-CMCTS-VES corresponding 1:10,2:10 and 3:10,and the corresponding EEs were 64.3%,74.5%and 39.7%.Cytotoxicity test,hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo.Drug release experiments implied good pH sensitivity and sustained-release effect.The DOX/O-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%.In the in vivo study by using H22 cells implanted Balb/C mice,DOX/O-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%.The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.
