Synthesis of Fluoridated Polymer for Self-assembly Nanovaccines with Antigen and Oligodeoxynucleotides for Cancer Immunotherapy

Cancer immunotherapy represents a type of cancer treatment that represses the disease by triggering immune responses. Cancer vaccines play a crucial role in this approach by delivering tumor-specific antigens into antigen-presenting cells which causes an antigen-specific immune response to eliminate cancer cells by effective delivery of antigens into antigen-presenting cells. Effective antigen presentation is critical in eliciting antigen-specific immune responses. Polymers such as dendrimers and polyethyleneimines (PEIs) have been reported for their potential application in delivering antigens and have functioned as vaccine vehicles. However, the cytotoxicity of PEI limits its application as a safe antigen-delivering vector. The fluorination effect can be utilized to reduce cytotoxicity and enhance the efficiency of antigen delivery by forming fluorinated PEI (F-PEI), which can be produced by fluorinating PEI with fluoroalkanes. Due to the low lipophobicity of modified fluoroalkyl chains on polymers, F-PEIs-based nanovaccine for delivering the model antigen ovalbumin (OVA) along with a vaccine adjuvant can induce antigen-specific immune responses targeting cancer. The F-PEI is capable of loading OVA and CpG oligonucleotides (CpG ODN) through electrostatic attraction. The resulting nanovaccine — F-PEI/OVA/CpG — exerts negligible effects on cell viability and effectively enters antigen-presenting cells. According to the observation, F-PEI/OVA/CpG activates bone marrow dendritic cells (BMDCs)’ maturation by upregulating the expression of CD80 protein and CD86 protein, which serve as mature markers for BMDCs. Future research related to F-PEI/OVA/CpG could be extended to different antigens (e.g., neoantigens) and potential clinical applications.