Acta Chimica Sinica ›› 2021, Vol. 79 ›› Issue (8): 1023-1029.DOI: 10.6023/A21050203 Previous Articles     Next Articles

Special Issue: 分子探针、纳米生物学与生命分析化学



王苏杭a, 孙灵娜a, 曹涵b, 钟一鸣c, 邵正中b,*()   

  1. a 深圳大学 化学与环境工程学院 深圳 518060
    b 复旦大学 聚合物分子工程国家重点实验室 先进材料实验室 高分子科学系 上海 200433
    c Babel International College, Perth, WA 6100, Australia
  • 投稿日期:2021-05-10 发布日期:2021-06-28
  • 通讯作者: 邵正中
  • 基金资助:
    国家自然科学基金(21704066); 国家自然科学基金(21935002); 广东省基础与应用基础研究基金项目(2021A1515010241); 深圳市高等院校稳定支持计划面上项目(20200813081943001)

Development of a Dual-drug-loaded Silk Fibroin Hydrogel and Study on Its Drugs Release Behaviors

Suhang Wanga, Lingna Suna, Han Caob, Yiming Zhongc, Zhengzhong Shaob()   

  1. a College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China
    b State Key Laboratory of Molecular Engineering of Polymers, Laboratory of Advanced Materials, Department of Macromolecular Science, Fudan University, Shanghai 200433, China
    c Babel International College, Perth, WA 6100, Australia
  • Received:2021-05-10 Published:2021-06-28
  • Contact: Zhengzhong Shao
  • Supported by:
    National Natural Science Foundation of China(21704066); National Natural Science Foundation of China(21935002); Guangdong Basic and Applied Basic Research Foundation(2021A1515010241); Shenzhen Natural Science Fund (the Stable Support Plan Program)(20200813081943001)

Injectable hydrogels, as an effective vehicle for localized drug delivery, have attracted increasing attention in recent years. With improved tumor-specific drug accumulation and lowered risk of infection, the application of in situ-forming injectable hydrogels provides an alternative to surgical implantation. In this study, based on a unique feature of regenerated silk fibroin (RSF) that it can easily form β-sheet structures, which function as physical cross-links, under various conditions, we designed an injectable silk fibroin hydrogel which encapsulated SBA-15 for the co-delivery of a vascular disrupting agent, combretastatin A4 disodium phosphate (CA4P), and doxorubicin hydrochloride (DOX). Such a CA4P and DOX co-encapsulated hydrogel ((RSF/CA4P)-(SBA-15/DOX)), simply prepared through a designed ultrasonication procedure, showed two different types of drug release behavior. CA4P was rapidly released, and it not only targeted the abnormal vasculature of tumors, causing vascular collapse, but also inhibited tumor cell proliferation by binding to tubulin and arresting mitosis. On the other hand, the sustained release of DOX can inhibit the proliferation of tumor cells for a prolonged period of time. Because of the rapid disruption of tumor vasculature and sustained inhibition of tumor cells proliferation, the (RSF/CA4P)-(SBA-15/DOX) hydrogel showed significantly enhanced cytotoxicity against human breast carcinoma cells (MDA-MB-231). By using this co-delivery system, the required dose of DOX can be lowered, and at the same time, the superior antitumor efficacy of the drugs is maintained. Our results suggest that the application of silk fibroin hydrogels to the co-delivery of a vascular disrupting agent and a chemotherapeutic agent with different drug release behaviors is a promising strategy in tumor treatment. Moreover, after sonication, the hydrogel precursor of (RSF/CA4P)-(SBA-15/DOX), can reach target irregular-shaped tumor sites via intratumor injection, and the hydrogels then form in situ, simply induced by body heat. Such silk fibroin-based hydrogels are injectable and malleable and fluorescent in dark field, which greatly facilitates their biomedical applications.

Key words: biomacromolecule, silk fibroin, hydrogel, injectable, dual-drug release behavior