Doxorubicin conjugated phospholipid prodrugs as smart nanomedicine platforms for cancer therapy

Haibo Wang; Xiangsheng Liu; Yin Wang; Yangjun Chen; Qiao Jin; Jian Ji

doi:10.1039/C4TB01984A

Doxorubicin conjugated phospholipid prodrugs as smart nanomedicine platforms for cancer therapy

Haibo Wang,^a Xiangsheng Liu,^a Yin Wang,^a Yangjun Chen,^a Qiao Jin*^a and Jian Ji*^a

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* Corresponding authors

^a MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
E-mail: jijian@zju.edu.cn, jinqiao@zju.edu.cn
Fax: +86-571-87953729
Tel: +86-571-87953729

Abstract

Ideal drug delivery systems should have prolonged circulation in blood, high accumulation in tumors with fast cellular uptake and burst drug release in cancer cells. Herein, a pH-sensitive small-molecule phospholipid prodrug based on phosphorylcholine (PC) was designed to overcome these challenges. The prodrug was synthesized by conjugating doxorubicin (DOX) to 11-mercaptoundecyl phosphorylcholine via an acid-labile hydrazone linker (UnPC-hyd-DOX). This phospholipid prodrug can self-assemble into core–shell micelles with exact and very high drug loading content (56.2%). Interestingly, the PC prodrug micelles can strongly minimize nonspecific phagocytosis by macrophages. They exhibited better ability to be internalized by cancer cells than that of the PEG prodrug micelles, which indicated that the PC shell facilitated cancer cell internalization. Moreover, in vitro results further demonstrated that DOX of phospholipid prodrug micelles can effectively escape from endo/lysosomes to the cytosol and enter the nucleus. An in vivo study demonstrated that these PC prodrug micelles exhibited much lower cardiotoxicity than free DOX. Importantly, PC prodrug micelles showed significantly slower blood clearance than PEG prodrug micelles and free DOX.

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Publication details

The article was received on 01 Dec 2014, accepted on 23 Feb 2015 and first published on 27 Feb 2015

Article type: Paper

DOI: 10.1039/C4TB01984A

Citation: J. Mater. Chem. B, 2015,3, 3297-3305

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Doxorubicin conjugated phospholipid prodrugs as smart nanomedicine platforms for cancer therapy

H. Wang, X. Liu, Y. Wang, Y. Chen, Q. Jin and J. Ji, J. Mater. Chem. B, 2015, 3, 3297
DOI: 10.1039/C4TB01984A
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Journal of Materials Chemistry B

Doxorubicin conjugated phospholipid prodrugs as smart nanomedicine platforms for cancer therapy

Abstract

Supplementary files

Publication details

Doxorubicin conjugated phospholipid prodrugs as smart nanomedicine platforms for cancer therapy

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