Poly(2-ethyl-2-oxazoline)鈥揇oxorubicin Conjugate-Based Dual Endosomal pH-Sensitive Micelles with Enhanced Antitumor Efficacy

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• 作者：Jinwen Li ; Yanxia Zhou ; Chengwei Li ; Dishi Wang ; Yajie Gao ; Chao Zhang ; Lei Zhao ; Yushu Li ; Yan Liu ; Xinru Li
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：January 21, 2015
• 年：2015
• 卷：26
• 期：1
• 页码：110-119
• 全文大小：531K
• ISSN：1520-4812

文摘

Dual endosomal pH-sensitive micelles were designed and fabricated to deliver doxorubicin (DOX) for treating breast cancer based on a poly(2-ethyl-2-oxazoline) (PEOz)鈥揇OX (PEOz鈥揾yd鈥揇OX) conjugate. PEOz鈥揾yd鈥揇OX was successfully synthesized by connecting DOX to PEOz via an acid cleavable hydrazone linker and self-assembled into nanosized micelles, which further physically encapsulated DOX. The conjugate and DOX-loaded conjugate micelles displayed faster release of DOX at pH 5.0 than at pH 7.4. This pH-dependent release behavior might assist the quick diffusion of DOX from acidic endosomes or lysosomes and the intracellular transfer into the nucleus after internalization, which was confirmed by confocal laser scanning microscopy images. As expected, PEOz鈥揾yd鈥揇OX conjugate and DOX-loaded conjugate micelles maintained cytotoxicity of DOX. In addition, the dual endosomal pH-sensitive micelles were found to substantially enhance antitumor efficacy and reduce side effects compared with free DOX. Therefore, PEOz鈥揾yd鈥揇OX conjugate-based micelles might be potential drug delivery vehicles of DOX for safe and effective breast cancer therapy.