Elastic Nanovaccine Enhances Dendritic Cell‐Mediated Tumor Immunotherapy. Issue 32 (22nd June 2022)

• Record Type: Journal Article
• Authors: Li, Qiang; Teng, Zhaogang; Tao, Jun; Shi, Wenhui; Yang, Guangwen; Zhang, Yu; Su, Xiaodan; Chen, Lin; Xiu, Weijun; Yuwen, Lihui; Dong, Heng; Mou, Yongbin
• Is Part Of: Small. Volume 18:Issue 32(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-22
• Subjects: dendritic cells -- elasticity -- mesoporous materials -- nanovaccines -- tumor immunotherapy; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202201108
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Nanovaccine‐based immunotherapy (NBI) has the ability to initiate dendritic cell (DC)‐mediated tumor‐specific immune responses and maintain long‐term antitumor immune memory. To date, the mechanism by which the mechanical properties of nanoparticles alter the functions of DCs in NBI remains largely unclear. Here, a soft mesoporous organosilica‐based nanovaccine (SMONV) is prepared and the elasticity‐dependent effect of the nanovaccine on the underlying DC‐mediated immune responses is studied. It is found that the elasticity results in greater internalization of SMONV by DCs, followed by the induction of substantial cytosolic delivery of antigens via endosomal escape, leading to effective DC maturation and antigen cross‐presentation. Impressively, elasticity enables SMONV to enhance lymphatic drainage of antigens in vivo, thus stimulating robust humoral and cellular immunity. The results from therapeutic tumor vaccination further reveal that subcutaneously administered SMONV effectively suppresses tumor growth in tumor‐bearing mice by evoking antigen‐specific CD8 + T‐cell immune responses, mitigating regulatory T‐cell‐mediated immunosuppression, and increasing central memory and effector memory T‐cell populations. Furthermore, combinatorial immunization with SMONV and anti‐PD‐L1 blocking antibodies results in an amplified therapeutic effect on tumor‐bearing mice. These findings reveal the elastic effect of the nanovaccine on DC‐mediated immune responses, and the prepared SMONV represents a facile and powerful strategy for antitumor immunotherapy. Abstract : The elastic nanovaccine soft mesoporous organosilica‐based nanovaccine (SMONV) effectively promotes lymphatic drainage, cellular internalization in dendritic cells (DCs), substantial cytosolic delivery of antigens, DC maturation, antigen cross‐presentation, tumor‐specific T‐cell immune responses, and inhibits Treg‐mediated immunosuppression, leading to superior antitumor efficacy.