Affiliation:
1. Tianjin Key Laboratory of Biomedical Materials Institute of Biomedical Engineering Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin 300192 China
2. Key Laboratory of Functional Polymer Materials Ministry of Education College of Chemistry Nankai University Tianjin 300071 China
3. Department of Biomedical Engineering University of Minnesota 7–105 Hasselmo Hall, 312 Church Street S. E. Minneapolis MN 55455 USA
Abstract
AbstractNanovaccines 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. Herein, reactive self‐assembly is used 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 groups and thiolated OVA results in the formation of nanoparticles with narrow size distribution. High OVA loading (≈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.
Funder
National Natural Science Foundation of China
Subject
Materials Chemistry,Polymers and Plastics,Organic Chemistry