Interface-sensitized prodrug nanoaggregate as an effective in situ antitumor vaccine
Yaxin Zheng1, Qi Li1, Qiulin Xu1
1School of Pharmacy, Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs, Chengdu Medical College, Chengdu, China.
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.
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.
