Hydrophilic Ethylene Glycol Fragments: A Determinant Affecting the Therapeutic Index of Paclitaxel Prodrug Nanoassemblies

IF 12.7 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Central Science Pub Date : 2024-11-20 DOI:10.1021/acscentsci.4c0100410.1021/acscentsci.4c01004

Yaqi Li, Yixin Sun, Qing Wang, Shuo Wang, Cuiyun Liu, Yuetong Huang, Wenxin Zhong, Xiyan Wang, Wenjing Wang, Shiyi Zuo, Xianbao Shi, Xiaohui Pu, Jin Sun, Zhonggui He* and Bingjun Sun*,

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引用次数: 0

Abstract

Prodrug-based nanoassemblies are promising platforms for cancer therapy. Prodrugs typically consist of three main components: drug modules, intelligent response modules, and modification modules. However, the available modification modules are usually hydrophobic aliphatic side chains, which affect the activation efficiency of the prodrugs. Herein, hydrophilic ethylene glycol fragments were inserted between the modification modules and the response modules, and the important effects of hydrophilic fragments on the assembly, drug release, and therapeutic index of the prodrugs were investigated. Notably, the introduction of hydrophilic fragments affected the intermolecular forces of the prodrugs and increased the interaction of hydrogen bonding. In addition, hydrophilic fragments significantly improved the redox drug release profiles, which affected the therapeutic index of the prodrug nanoassemblies. PTX-SS-OA NPs with hydrophilic fragments exhibited increased redox sensitivity, enhanced cytotoxicity, and superior antitumor efficacy. In comparison, PTX-SS-OAL NPs without hydrophilic fragments showed limited redox sensitivity and cytotoxicity but displayed better safety. Overall, the hydrophilic fragment is a critical determinant in modulating the therapeutic index of the prodrug nanoassemblies, which contributes to the development of advanced prodrug nanodelivery systems.

Hydrophilic ethylene glycol fragment is a critical determinant in modulating the therapeutic index of the paclitaxel prodrug nanoassemblies.

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来源期刊

ACS Central Science Chemical Engineering-General Chemical Engineering

CiteScore

25.50

自引率

0.50%

发文量

194

审稿时长

10 weeks

期刊介绍： ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.