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The Construction And Application Of Natural Tempo-Oxidized Starch Nanoassemblies

Posted on:2019-10-22Degree:MasterType:Thesis
Country:ChinaCandidate:Y M JiangFull Text:PDF
GTID:2371330551957270Subject:Pharmacy
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Many synthetic polymers used for drug delivery will accumulate in tissues after cell death or exocytosis without complete biodegradation,but these excessive accumulations of potential toxicity in normal tissues and organs cannot be ignored.Therefore,there is an urgent need to develop nanocarriers with excellent biocompatibility,good degradability and low toxicity in living organismsEnhancing delivery efficiency of anticancer drug and improving the antitumor treatment effect has been a hot topic in recent years.Surface-modified with targeting peptide can greatly increase the retention and accumulation of nanocarrier in the tumor vasculature and reduce their side effects on normal tissues and organs.In this paper,TEMPO-oxidized starch nanoassemblies modified with targeting peptide are developed and investigated.The main results are as follows:1.Preparation and characterization of TEMPO-oxidized starch nanoassemblies.The results show that oxidized starch can form 30-50 nm uniform,well dispersed nanoassemblies in the physiological conditions.TEMPO-oxidized starch nanoassemblies are pH responsive and have potential to be developed as an anticancer drug carrier.2.Targeted modification and toxicity of oxidized starch.TEMPO-oxidized starch nanoassemblies are modified with PEG and targeting peptide RGD,and the morphology is remained after modification.As a structural analogue,PAA exhibits a high cytotoxicity,severe liver and spleen toxicity,and slight nephrotoxicity.While TEMPO-oxidized starch nanoassemblies exhibits negligible toxicity in several cell lines and ICR mice.The results suggest that TEMPO-oxidized starch nanoassemblies could be used as a new type of carrier material that can replace PAA.3.Biological characterization of tumor-targeted TEMPO-oxidized starch nanoassemblies.The DOX-loaded tumor-targeted TEMPO-oxidized starch nanoassemblies can efficiently target HepG2 cells,increase the accumulation in HepG2 tumors,inhibit the growth of HepG2 tumors and have no significant negative effects on normal tissues and organs.In summary,TEMPO-oxidized starch nanoassemblies are pH-responsive and have a negligible toxicity.The nanoassemblies modified with targeting peptide exhibit high efficiency in suppressing HepG2 tumor growth without significant negative effects on normal tissues and organs,which suggests a bright application prospect.
Keywords/Search Tags:nanoassemblies, TEMPO-oxidized starch polymer, targeted delivery, cancer therapy, DOX
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