期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 164, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejps.2021.105910
关键词
In situ antitumor vaccines; Lipid-drug conjugate; Toll-like receptor; Cationic; Intratumoral
资金
- Sichuan Science and Technology Program [2019YJ0068]
- Foundation for New Teacher Training Program of Chongqing Medical University [YXY2020XSZ02]
The study introduces a simple and effective in situ antitumor vaccine prepared by co-assembling lipid-drug conjugates, demonstrating faster drug release and potential for potent in vivo antitumor immune responses.
In situ antitumor vaccines have been widely explored as an effective strategy to inhibit tumor growth by stimulating antitumor immune responses. Herein, we reported a simple and effective in situ antitumor vaccine, which was prepared by co-assembling cationic lipids (DOTAP) with the disulfide bond-linked lipid-drug conjugates of camptothecin and resiquimod. The resulting vaccine had a rod-sharped morphology with nanoscale sizes (average hydrodynamic diameter of -163.7 nm) and positively-charged interfaces (zeta potential - +36.2 mV). The interfacial cationization of nanoaggregate resulted in 1000 folds faster redox-responsive drug release than that of unmodified ones, which induced a much more potent in vivo antitumor immune by accelerating the glutathione-responsive drug release at the tumor site. Such cationic lipid-drug nanoaggregates displayed many benefits, such as high co-loading capacity, simple preparation process, and wide applicability, which would serve as a promising new approach to design effective in situ antitumor vaccines.
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