Glycopolypeptide Coordinated Nanovaccine: Fabrication, Characterization, and Antitumor Immune Response.

Abstract

Cancer nanovaccine is a frontier immunotherapy strategy, in which the delivery carrier can protect antigen and adjuvant from degradation, increase blood circulation half-life, and improve antigen permeability and presentation, thus enhancing the security and potency of nanovaccine. To address the barriers of antigen delivery, we design and fabricate a kind of intracellular pH-sensitive glycopolypeptide coordinated nanovaccine (OVA-HPGM-Mn) with ∼30% loading capacity of ovalbumin (OVA). The nanovaccine OVA-HPGM-Mn could specifically deliver antigen to dendritic cells (DCs) and effectively escape from endolysosomes to cytoplasm after 6 h of incubation, while the blank counterpart HPGM-Mn acted as an adjuvant to promote DCs maturation and increase the percentage of maturated cells to 26.5% from 11.8% in vitro. Furthermore, the mannosylated polypeptide nanovaccine prolonged the retention time of OVA for 72 h to facilitate 29.5% DCs maturation in lymph nodes, activated 48.8% CD8⁺T cells in spleen, increased the CD8⁺/CD4⁺T cell ratio twice to 1.06, and upregulated the levels of pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-6, thus inhibiting the tumor growth of ∼80%. Consequently, this work provides a versatile strategy for the fabrication of glycosylated polypeptide coordinated nanomaterials for antigen delivery and cancer immunotherapy.