Construction of Targeting-Clickable and Tumor-Cleavable Polyurethane Nanomicelles for Multifunctional Intracellular Drug Delivery

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• 作者：Nijia Song ; Mingming Ding ; Zhicheng Pan ; Jiehua Li ; Lijuan Zhou ; Hong Tan ; Qiang Fu
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：December 9, 2013
• 年：2013
• 卷：14
• 期：12
• 页码：4407-4419
• 全文大小：877K
• 年卷期：v.14,no.12(December 9, 2013)
• ISSN：1526-4602

文摘

New strategies for the construction of versatile nanovehicles to overcome the multiple challenges of targeted delivery are urgently needed for cancer therapy. To address these needs, we developed a novel targeting-clickable and tumor-cleavable polyurethane nanomicelle for multifunctional delivery of antitumor drugs. The polyurethane was synthesized from biodegradable poly(蔚-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by a new designed l-cystine-derivatized chain extender bearing a redox-responsive disulfide bond and clickable alkynyl groups (Cys-PA), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with a highly pH-sensitive benzoic-imine linkage (BPEG). The obtained polymers show attractive self-assembly characteristics and stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). Furthermore, folic acid (FA) as a model targeting ligand was conjugated to the polyurethane micelles via an efficient click reaction. The decoration of FA results in an enhanced cellular uptake and improved drug efficacy toward FA-receptor positive HeLa cancer cells in vitro. As a proof-of-concept, this work provides a facile approach to the design of extracellularly activatable nanocarriers for tumor-targeted and programmed intracellular drug delivery.