期刊
CARBOHYDRATE POLYMERS
卷 291, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2022.119671
关键词
Carboxymethyl chitosan; Prodrugs; Dynamic change; Synergistic chemotherapy
资金
- National Natural Science Foundation of China [51803001]
- Research Foundation of Education Department of Anhui Province of China [KJ2018ZD003, KJ2018A0006, KJ2019A0015]
- Academic and Technology Introduction Project of Anhui University [AU02303203]
The development of polysaccharide-based nano-prodrug with stimuli-responsive and synergetic effect is highly demanded. The dynamic carboxymethyl chitosan (CMCS)-based nano-prodrugs with precise structure were successfully fabricated, showing tumor selectivity and excellent stability. The pH/glutathione (GSH)-responsive double-crosslinked structure enabled long-term storage, circulation stability, and selective drug release at tumor sites, leading to robust tumor suppression and decreased side effects.
Currently, the polysaccharide-based nano-prodrug crosslinked by stimuli-responsive synergetic prodrug is of great demand, owing to its excellent stability, synergetic effect and tumor selectivity, and circumventing the dilemma of dose-limiting toxicity and immunogenicity induced by that crosslinked or grafted via a single drug. Herein, the dynamic carboxymethyl chitosan (CMCS)-based nano-prodrugs with precise structure were facilely fabricated, via crosslinking reaction between CMCS and water-soluble synergistic small molecule prodrug (cisplatin-demethylcantharidin conjugate) and further stabilization by glutaraldehyde. The pH/glutathione (GSH)-responsive double-crosslinked structure endowed the nano-prodrugs with long-term storge and circulation stability at physiological pH, and dynamic transitions at tumor sites including extracellular surface amino protonation and intracellular efficient drug release, which promoted selective tumor accumulation and synergistic cytotoxicity, therefore achieving robust tumor suppression while decreasing side effects. Thus, the dynamic precise CMCS-based nano-prodrugs crosslinked by water-soluble synergistic prodrug have great potential for highly selective robust chemotherapy attractive for clinical translation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据