title: Precise Polymerization of a Highly Tumor Microenvironment-Responsive Nanoplatform for Strongly Enhanced Intracellular Drug Release.
abstract: The importance of achieving a high content of responsive groups of drug carriers is well-known for achieving rapid intracellular drug release; however, very little research has been published on this subject. Here, we present an entirely new strategy to synthesize a highly reduction-sensitive polymer-drug conjugate with one disulfide bond corresponding to each resultant copolymer through a precise ring-opening polymerization of ε-caprolactone that is initiated by a monoprotected cystamine. Simultaneously, the anticancer drug doxorubicin is chemically conjugated to the polymer via pH-responsive hydrazone bonds, which effectively prevent premature drug release in the blood circulation. The 3-aminophenylboronic acid (PBA) targeting ligands endow an active-targeting ability that significantly prompts the specific internalization of nanocarriers by tumor cells and thus results in excellent cytotoxicity against tumor cells. The concept of precise polymerization is put forward to achieve multifunctional nanocarriers for the first time. This study is expected to inspire the development of a highly environment-responsive nanoplatform for drug delivery in future clinical applications.
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu, Sichuan610031, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu, Sichuan610031, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu, Sichuan610031, P.R. China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu, Sichuan610031, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu, Sichuan610031, P.R. China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu, Sichuan610031, P.R. China.
authors.forename: Shaobing
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002208:Caproates / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000737:chemistry; D008297:Male; D051379:Mice; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D002208:Caproates; D004220:Disulfides; D004337:Drug Carriers; D007783:Lactones; D008823:Micelles; D011108:Polymers; C121056:caprolactone; D004317:Doxorubicin
keywords: cancer therapy; nanoplatform; precise polymerization; reduction-responsive; ultrasensitive