A novel multifunctional vaccine platform with dendritic cell-targeting and pH-responsive for cancer immunotherapy: Antigen-directed biomimetic fabrication of a cabbage-like mannatide-zinc-antigen hybrid microparticles

Abstract

Cancer vaccines, featuring with high-specificity and long-term immune memory effect, have received tremendous attention in the field of cancer immunotherapy. However, most current developed antigen-encapsulated multifunctional cancer vaccines are subjected to limited antigen loading capacity, low yield, complicated preparation process, inefficient antigen delivery, and potential systemic toxicity. Herein, a facile biomimetic strategy is reported to fabricate a multifunctional cancer vaccine with high antigen loading capacity, dendritic cells-targeting and pH-responsive. As a proof of strategy, we directly use model antigen ovalbumin (OVA) and dendritic cells-targeting molecule mannatide as organic templates, zinc (II) as inorganic component to construct antigen and mannatide co-loaded hybrid microparticles vaccine. These formed mannatide-zinc-ovalbumin hybrid microparticles (M-Zn-OVA HMPs) owns cabbage-like morphology with particle size of ~1.7 μm, high antigen loading capacity of 11.7%, high yield of 84.6%, good stability, and favorable biocompatibility. Taking advantage of high antigen loading, pH-responsive, and dendritic cells-targeting molecule, M−Zn−OVA HMPs can target deliver antigen to dendritic cells, and effectively maturation of dendritic cells to induce robust immune responses. As a result, such M−Zn−OVA HMPs shows outstanding prophylactic efficacy toward B16-OVA and E.G7-OVA tumors. Moreover, M−Zn−OVA HMPs demonstrates excellent therapeutic efficacy against established B16-OVA and E.G7-OVA tumors, and the therapeutic efficacy can be further enhanced when used in combination with anti-programmed death-1 (anti-PD-1) checkpoint blockade. Therefore, our work may present a facile and versatile strategy for large-scale fabrication of multifunctional vaccines for cancer immunotherapy.