Poly(2-ethyl-2-oxazoline)-doxorubicin conjugate-based dual endosomal pH-sensitive micelles with enhanced antitumor efficacy.
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| Abstract |
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)-DOX (PEOz-hyd-DOX) conjugate. PEOz-hyd-DOX 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-hyd-DOX 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-hyd-DOX conjugate-based micelles might be potential drug delivery vehicles of DOX for safe and effective breast cancer therapy.
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| Authors | Jinwen Li, Yanxia Zhou, Chengwei Li, Dishi Wang, Yajie Gao, Chao Zhang, Lei Zhao, Yushu Li, Yan Liu, Xinru Li |
| Journal | Bioconjugate chemistry (Bioconjug Chem) Vol. 26 Issue 1 Pg. 110-9 (Jan 21 2015) ISSN: 1520-4812 [Electronic] United States |
| PMID | 25506713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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