Sodium cholesterol sulfate mediated mitoxantrone prodrug electrostatic nanocomplexes: achieving the therapeutic efficacy and safety of mitoxantrone

IF 10.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Science China Chemistry Pub Date : 2024-10-21 DOI:10.1007/s11426-024-2251-3

Erwei Zhao, Lingxiao Li, Jingyi Zhang, Yaqiao Li, Rong Chai, Bowen Zhang, Jialin Xing, Minglong Huang, Lurong Zhang, Xiaohui Pu, Zhonggui He, Bingjun Sun

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引用次数: 0

Abstract

Forming electrostatic nanocomplexes (ENCs) with counter-ions can improve the delivery efficiency of chemotherapy drugs. However, water-soluble chemotherapy drugs like mitoxantrone (MTO), have limited affinity for counter-ions, posing challenges in the creation of stable ENCs. Herein, MTO was connected to fatty alcohols of varying chain lengths (C8, C12, C16) via disulfide bonds, forming hydrophobic prodrugs. We found that conjugating MTO to fatty alcohols significantly improved its affinity for the counter-ion sodium cholesterol sulfate (SCS). Among the designed prodrugs, conjugated to fatty alcohols with longer carbon chain lengths exhibited heightened affinity for SCS, resulting in the formation of more stable ENCs. However, extending the carbon chain also slowed the rate of drug release. Overall, compared with MTO solution, these ENCs demonstrated comparable therapeutic efficacy while causing minimal damage to healthy tissues, especially for MTO-SS-C16 ENCs. Our research provides new insights for constructing stable and safe ENCs for hydrophilic drugs like MTO.

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来源期刊

Science China Chemistry CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

14.40

自引率

7.30%

发文量

3787

审稿时长

2.2 months

期刊介绍： Science China Chemistry, co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China and published by Science China Press, publishes high-quality original research in both basic and applied chemistry. Indexed by Science Citation Index, it is a premier academic journal in the field. Categories of articles include: Highlights. Brief summaries and scholarly comments on recent research achievements in any field of chemistry. Perspectives. Concise reports on thelatest chemistry trends of interest to scientists worldwide, including discussions of research breakthroughs and interpretations of important science and funding policies. Reviews. In-depth summaries of representative results and achievements of the past 5–10 years in selected topics based on or closely related to the research expertise of the authors, providing a thorough assessment of the significance, current status, and future research directions of the field.