Aptamer-Functionalized and Backbone Redox-Responsive Hyperbranched Polymer for Targeted Drug Delivery in Cancer Therapy.
A novel type of backbone redox-responsive hyperbranched poly(2-((2-(acryloyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(((propylthio)carbonothioyl)-thio)-pentanoate-co-poly(ethylene glycol) methacrylate) (HPAEG) has been designed and prepared successfully via the combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization and self-condensing vinyl polymerization (SCVP). Owing to the existence of surface vinyl groups, HPAEG could be efficiently functionalized by DNA aptamer AS1411 via Michael addition reaction to obtain an active tumor targeting drug delivery carrier (HPAEG-AS1411). The amphiphilic HPAEG-AS1411 could form nanoparticles by macromolecular self-assembly strategy. Cell Counting Kit-8 (CCK-8) assay illustrated that HPAEG-AS1411 nanoparticles had low cytotoxicity to normal cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) results demonstrated that HPAEG-AS1411 nanoparticles could be internalized into tumor cells via aptamer-mediated endocytosis. Compared with pure HPAEG nanoparticles, HPAEG-AS1411 nanoparticles displayed enhanced tumor cell uptake. When the HPAEG-AS1411 nanoparticles loaded with anticancer drug doxorubicin (DOX) were internalized into tumor cells, the disulfide bonds in the backbone of HPAEG-AS1411 were cleaved by glutathione (GSH) in the cytoplasm, so that DOX was released rapidly. Therefore, DOX-loaded HPAEG-AS1411 nanoparticles exhibited a high tumor cellular proliferation inhibition rate and low cytotoxicity to normal cells. This aptamer-functionalized and backbone redox-responsive hyperbranched polymer provides a promising platform for targeted drug delivery in cancer therapy.
Yuanyuan
Y
Zhuang
Hongping
H
Deng
Yue
Y
Su
Lin
L
He
Ruibin
R
Wang
Gangsheng
G
Tong
National Engineering Research Center for Nanotechnology, 28 East Jiang Chuan Road, Shanghai 200241, People's Republic of China.
Dannong
D
He
Xinyuan
X
Zhu
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D065546:Drug Liberation; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry
C513936:AGRO 100; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; C000623213:HPAEG polymer; D009838:Oligodeoxyribonucleotides; D011109:Polymethacrylic Acids; D004317:Doxorubicin