Photodynamic therapy (
PDT) is an effective, noninvasive 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 antitumor 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 coloaded into a 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 cytotoxic T-cell lymphocytes. Using multiple murine models of bilateral
tumors, we demonstrate strong antitumor efficacy of
PDT-
immunotherapy against locally treated
tumors as well as distant, untreated
tumors. Our findings suggest that the bMSN is a promising platform for combining imaging and
PDT-enhanced personalized
immunotherapy for the treatment of advanced
cancer.