Polymer-Protein Nanovaccine Synthesized via Reactive Self-Assembly with Potential Application in Cancer Immunotherapy: Physicochemical And Biological Characterization In Vitro And in Vivo.

Nanovaccines composed of polymeric nanocarriers and protein-based antigens have attracted much attention in recent years because of their enormous potential in the prevention and treatment of diseases such as viral infections and cancer. While surface-conjugated protein antigens are known to be more immunoactive than encapsulated antigens, current surface conjugation methods often result in low and insufficient protein loading. Here, we use reactive self-assembly to prepare nanovaccine from poly(ε-caprolactone) (PCL) and ovalbumin (OVA) - a model antigen. A rapid thiol-disulfide exchange reaction between PCL with pendant pyridyl disulfide (PDS) groups and thiolated OVA results in the formation of nanoparticles with narrow size distribution. High OVA loading (approximately 70 - 80 wt %) is achieved, and the native secondary structure of OVA is preserved. Compared to free OVA, the nanovaccine is much superior in enhancing antigen uptake by bone marrow-derived dendritic cells (BMDCs), promoting BMDC maturation and antigen presentation via the MHC I pathway, persisting at the injection site and draining lymph nodes, activating both Th1 and Th2 T cell immunity, and ultimately, resisting tumor challenge in mice. This is the first demonstration of reactive self-assembly for the construction of a polymer-protein nanovaccine with clear potential in advancing cancer immunotherapy. This article is protected by copyright. All rights reserved.