Background
By leveraging the power of photodynamic therapy (PDT), photosensitizers eliminate cancer cells under specific laser irradiation and trigger systemic immune responses, a potent strategy in tumor immunotherapy. However, the accompanying tumor microenvironment induces immunosuppression, restricting the efficacy of PDT.
Conclusion
Our research findings demonstrate that the nanoparticles formed by the computer-aided screened adjuvant, Vit K2, and the photosensitizer PPA achieved significant anti-tumor activity and immune microenvironment remodeling.
Methods
Computer-aided screening was used to identify adjuvants, followed by flow cytometry analysis to assess the activation levels of various immune cells in both in vitro and in vivo experiments. Cytotoxicity assays were conducted to evaluate the impact of the nanomaterials on tumor cells. Pharmacokinetic studies were performed to observe the drug concentration in vivo. The efficacy of the nanomaterials was further tested using in situ tumor, metastasis, and organoid models.
Results
we first utilized computational simulations and experimental validations to identify Vit K2 as an adjuvant with a high affinity for Toll-like receptor (TLR) agonist ligands; Vit K2 effectively activated antigen-presenting cells, including dendritic cells (DCs) and macrophages, and promoted their maturation through the TLR pathways. The precisely engineered nanoamplifier with on-demand pyropheophorbide a (PPA) release ability could notably kill the primary tumor. Vit K2-activated macrophages and DCs matured, promoting antigen presentation and CD8+ T cell activation. As anticipated, the nanoamplifier exhibited significant anti-tumor effects in primary/distal breast tumors, lung metastatic breast cancer, and patient-derived organoid models.