Preparation and antitumor activity characterization of oncolytic nanoparticles encapsulating CVA21.
- Author:
Yinping WANG
1
;
Qiying CAI
2
;
Jingjing ZHOU
3
;
Xiaodi ZHENG
1
;
Linkang CAI
4
;
Yang WANG
1
;
Binlei LIU
1
Author Information
- Publication Type:Journal Article
- Keywords: Coxsackievirus A21 (CVA21); messenger ribonucleic acid (mRNA); oncolytic nanoparticles; tumor
- MeSH: Animals; Nanoparticles/chemistry*; Mice; Mice, Inbred BALB C; Humans; Apoptosis; Oncolytic Viruses/genetics*; Oncolytic Virotherapy/methods*; Cell Line, Tumor; RNA, Messenger/genetics*; HT29 Cells
- From: Chinese Journal of Biotechnology 2025;41(4):1395-1414
- CountryChina
- Language:Chinese
- Abstract: This study aims to investigate the potential of oncolytic nanoparticles encapsulating Coxsackievirus A21 (CVA21) full-genome mRNA (CVA21@ONP) to resurrect CVA21 and induce apoptosis in host cells, as well as the antitumor immune effects of CVA21@ONP in immunocompetent tumor-bearing BALB/c mice. We used lipid nanoparticles (LNPs) to encapsulate CVA21 full-genome mRNA, thus preparing CVA21@ONP. The killing efficacy of CVA21@ONP was determined by the plaque assay and cell counting kit-8 (CCK-8), and the apoptosis in HT29 and CT26-iRFP cells was evaluated by flow cytometry. Mice were administrated with CVA21@ONP at high and low doses intratumorally, and the growth of tumors expressing infra-red fluorescent protein (iRFP) was monitored. Additionally, the types and changes of immune cells in the spleen were analyzed by flow cytometry. The results demonstrated that CVA21@ONP successfully resurrected CVA21 in both HT29 and U87MG cells. The plaque assay revealed robust killing effects of CVA21@ONP against both human and murine cell lines, and flow cytometry results showed increased early and late apoptotic cells. Notably, intratumoral detection revealed significantly down-regulated expression of iRFP in both high- and low-dose CVA21@ONP groups. Flow cytometry results further indicated that CVA21@ONP treatment effectively reduced the levels of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), in the spleen, while enhancing T cell-dependent antitumor immune responses. These findings suggest that CVA21@ONP can replicate and survive extensively both in vitro and in vivo, activating the immune system of mice administrated with CVA21@ONP to target cells at the tumor site, thereby remodeling the tumor immune microenvironment and accelerating the suppression or even complete regression of tumors. The oncolytic performance of CVA21@ONP has been verified through intratumoral injection administration in this study, aimed at further exploring its therapeutic potential and promoting the development of the field of tumor treatment.
