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Issue 35, 2018
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Improving the carrier stability and drug loading of unimolecular micelle-based nanotherapeutics for acid-activated drug delivery and enhanced antitumor therapy

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Abstract

Nanomedicines based on unimolecular micelles (UMs) have shown unique advantages such as high micellar stability, programmed cargo delivery and enhanced therapeutic efficiency. Herein, we report an acid-activated amphiphilic prodrug based on a dextran (DEX) polymeric framework (DEX–PDOX-b-POEGMA, labelled DMO@DOX), which conjugates a diblock copolymer of a hydrophobic doxorubicin (DOX) prodrug block and a hydrophilic poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) block by atom transfer radical polymerization. The DMO@DOX prodrug can form nano-sized UMs in aqueous media attributed to its amphiphilic structure and achieve a very high drug loading rate of 80.4 wt%. In the presence of an acidic medium resembling a tumor microenvironment, the hydrazone bond embedded in the prodrug is broken, which releases the loaded drug of DOX. The DMO@DOX prodrug shows a notable and preferential inhibition effect on the growth of tumor cells in vitro compared to healthy cells, leading to advantageous biocompatibility and effective antitumor activity. For verification, the DMO@DOX prodrug was applied in the treatment of a mouse model bearing xenograft tumors and showed a remarkable therapeutic performance. This study demonstrates an effective design of UM-based nanoagents to improve the micellar stability of polymeric prodrug micelles with enhanced performance in cancer therapy.

Graphical abstract: Improving the carrier stability and drug loading of unimolecular micelle-based nanotherapeutics for acid-activated drug delivery and enhanced antitumor therapy

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Publication details

The article was received on 26 May 2018, accepted on 06 Aug 2018 and first published on 08 Aug 2018


Article type: Paper
DOI: 10.1039/C8TB01384E
Citation: J. Mater. Chem. B, 2018,6, 5549-5561
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    Improving the carrier stability and drug loading of unimolecular micelle-based nanotherapeutics for acid-activated drug delivery and enhanced antitumor therapy

    X. Shi, S. Bai, C. Yang, X. Ma, M. Hou, J. Chen, P. Xue, C. M. Li, Y. Kang and Z. Xu, J. Mater. Chem. B, 2018, 6, 5549
    DOI: 10.1039/C8TB01384E

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