Effect of NIR-II on cancer nanocomposite vaccines for lymph node targeted delivery and enhanced immunotherapy.

person HaiYu Zhou Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China info_outline HaiYu Zhou, YuCheng Huang, Bin Xu, HengLiang Hou

Authors person HaiYu Zhou Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China info_outline HaiYu Zhou, YuCheng Huang, Bin Xu, HengLiang Hou Organizations Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China, School of Medicine, South China University of Technology, Guangzhou, China, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, China Abstract Disclosures Research Funding No funding sources reported Background: Cancervaccines have become one of the hot areas of research in recent years. However, different types of tumors and the tumor tissue itself are heterogeneous. Some cancervaccines contain a single epitope and have weak immunogenicity. The antigen-presenting cells cannot adequately absorb and present the antigen peptide contained in the vaccine. As a result, the body fails to elicit an effective immune response, which greatly limits the therapeutic effect of the cancervaccine. In situ cancervaccines composed of antigens and adjuvants are a promising cancer treatment modality; however, convenient manufacturing of vaccines in vivo and their efficient delivery to lymph nodes (LNs) remain a significant challenge. In this study, we outline a facile approach to simultaneously achieve in situ programming of vaccines via two synergistic nanomedicines to generate robust immune responses. Methods: We first prepared two synergistic nanocomposite systems: Gold nanorods, amphiphilic polymer polyphosphate mPEG- b -PHEP encapsulating the immune adjuvant R848, and nanoparticles doped with cationic liposomes DOTAP. Two nanomedicines were characterized and the efficacy of the nanovaccine was verified at the Cellular Experiments. At the animal level, the lymph node targeting of the nanoparticles was demonstrated through IVIS. We also constructed distant model and lung metastasis model to verify the nanovaccine's effect on enhancing systemic immunotherapy. Results: We used amphiphilic polymer polyphosphate mPEG- b -PHEP to encapsulate TLR7/8 agonist R848 to obtain VNP R848 nanoparticles. Gold nanorods (~ 100nm) can produce a strong photothermal effect mediated by NIR-II, killing tumor cells and releasing abundant antigens at the same time. The small size of VNPR848 (~ 30nm) is beneficial to the enrichment of lymph nodes. After capturing the antigens produced by photothermal, nanoparticles will be targeted and delivered to the tumor draining lymph nodes together with R848, and will be effectively absorbed by DC cells. This in situ tumor vaccine with the ability of targeted delivery of lymph nodes can trigger a strong anti-tumor immune response. This therapy can completely inhibit distant tumors in some mice and produce a long-term immune memory effect on NSCLC metastasis. Conclusions: We propose a simple personalized in situ cancervaccine strategy, which uses nanotechnology to remove tumors in situ and release antigens. Antigens and immune adjuvants are simultaneously delivered to the draining lymph nodes to initiate the antigen presentation function of DC cells, resulting in an anti-tumor immune response to inhibit tumor recurrence and metastasis. The nano-vaccine based on powerful therapeutic effect provides an attractive technology for in situ programming of personalized cancervaccine and an effective strategy for the development of cancervaccine.

Pre-clinical