Improving the carrier stability and drug loading of unimolecular micelle-based nanotherapeutics for acid-activated drug delivery and enhanced antitumor therapy. Issue 35 (22nd August 2018)

• Record Type: Journal Article
• Authors: Shi, Xiaoxiao; Bai, Shuang; Yang, Cangjie; Ma, Xiaoqian; Hou, Meili; Chen, Jiucun; Xue, Peng; Li, Chang Ming; Kang, Yuejun; Xu, Zhigang
• Is Part Of: Journal of materials chemistry. Volume 6:Issue 35(2018)
• Page Start: 5549
• Page End: 5561
• Publication Date: 2018-08-22
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c8tb01384e
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : Nanomedicines based on unimolecular micelles (UMs) have shown unique advantages such as high micellar stability, programmed cargo delivery and enhanced therapeutic efficiency. 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.