An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer.
10.1016/j.apsb.2022.03.017
- Author:
Yunting ZHANG
1
;
Min JIANG
1
;
Guangsheng DU
1
;
Xiaofang ZHONG
1
;
Chunting HE
1
;
Ming QIN
1
;
Yingying HOU
1
;
Rong LIU
1
;
Xun SUN
1
Author Information
1. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- Keywords:
Antigen cross-presentation;
Cancer immunotherapy;
Cellular immunity;
Dendritic cell;
Mannose receptor;
Self-assembled nanovaccine;
Subunit antigen;
Zoledronic acid
- From:
Acta Pharmaceutica Sinica B
2023;13(8):3518-3534
- CountryChina
- Language:English
-
Abstract:
The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.
