International Journal of Nanomedicine (May 2023)
Cancer Cell Membrane-Coated Gambogic Acid Nanoparticles for Effective Anticancer Vaccination by Activating Dendritic Cells
Abstract
Fengli Huang,1,* Qun Zhang,2,* Jie Xiao,3,* Xin Zhang,1 Xingzhi Han,3 Xiao Shi,3 Jing Hu,2 Li Li,2 Xiaoping Qian1,2 1Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Oncology, Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 3Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping Qian, Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-13951743162, Fax +86-25-68182342, Email [email protected]: Recent studies have shown that traditional Chinese medicine (TCM), such as gambogic acid (GA), is involved in the regulation of tumor immune microenvironment and can be combined with other anti-tumor treatment strategies. Here, we used GA as an adjuvant to construct a nano-vaccine to improve the anti-tumor immune response of colorectal cancer (CRC).Materials and Methods: We used a previously reported two-step emulsification method to obtain poly (lactic-co-glycolic acid) /GA nanoparticles (PLGA/GA NPs), and then CT26 colon cancer cell membrane (CCM) was used to obtain CCM-PLGA/GA NPs. This novel nano-vaccine, CCM-PLGA/GA NPs, was co-synthesized with GA as an adjuvant and neoantigen provided by CT26 CCM. We further confirmed the stability, tumor targeting, and cytotoxicity of CCM-PLGA/GA NPs. The regulatory effect on the tumor immune microenvironment, the anti-tumor efficacy, and the combined anti-tumor efficacy with anti-PD-1 monoclonal Antibodies (mAbs) of this novel nano-vaccine was also detected in vivo.Results: We successfully constructed the CCM-PLGA/GA NPs. In vitro and in vivo tests showed low biological toxicity, as well as the high tumor-targeting ability of the CCM-PLGA/GA NPs. Besides, we revealed a remarkable effect of CCM-PLGA/GA NPs to activate the maturation of dendritic cells (DCs) and the formation of a positive anti-tumor immune microenvironment.Conclusion: This novel nano-vaccine constructed with GA as the adjuvant and CCM providing the tumor antigen can not only directly kill tumors by enhancing the ability of GA to target tumors, but also indirectly kill tumors by regulating tumor immune microenvironment, providing a new strategy for immunotherapy of CRC.Keywords: cancer immunotherapy, gambogic acid, nano-vaccine, tumor immune microenvironment, colorectal cancer
