Positron Emission Tomography-Guided Photodynamic Therapy with Biodegradable Mesoporous Silica Nanoparticles for Personalized Cancer Immunotherapy.

Photodynamic therapy (PDT) is an effective, non-invasive therapeutic modality against local tumors that are accessible to the source of light. However, it remains challenging to apply PDT for the treatment of disseminated, metastatic cancer. On the other hand, cancer immunotherapy offers a promising approach for generating systemic anti-tumor immune responses against disseminated cancer. Here we report a multifunctional nanomaterial system for the combination of PDT and personalized cancer immunotherapy and demonstrate their potency against local as well as disseminated tumors. Specifically, we have synthesized uniform and biodegradable mesoporous silica nanoparticles (bMSN) with an average size of ~80 nm and large pore size of 5-10 nm for theranostic positron emission tomography (PET)-guided PDT and neoantigen-based cancer vaccination. Multiple neoantigen peptides, CpG oligodeoxynucleotide adjuvant, and photosensitizer chlorin e6 were co-loaded into bMSN nanoplatform, and PET imaging revealed effective accumulation of bMSN in tumors (up to 9.0% ID/g) after intravenous administration. Subsequent PDT with laser irradiation recruited dendritic cells to PDT-treated tumor sites and elicited neoantigen-specific, tumor-infiltrating CTLs. Using multiple murine models of bilateral tumors, we demonstrate strong anti-tumor efficacy of PDT-immunotherapy against locally treated tumors as well as distant, untreated tumors. Our findings suggest that bMSN is a promising platform for combining imaging and PDT-enhanced personalized immunotherapy for the treatment of advanced cancer.