Innate immune activation by conditioned medium of cancer cells following combined phototherapy with photosensitizer-loaded gold nanorods.

Nanoparticle-based phototherapy has evolved to include immunotherapy as an effective treatment combination for cancers through inducing anti-cancer immune activation leading to downstream adaptive responses and immune protection. However, most cancer phototherapy studies that claimed anti-cancer immunogenic effects often included exogenous immunostimulants to potentiate immune responses and did not clearly establish their effects on immune cells. In this study, we showed that combined photodynamic (PDT) and photothermal therapy (PTT) using gold nanorods (NRs) loaded with the photosensitizer chlorin e6 (Ce6) on endogenously formed mouse serum (MS) protein coronas (i.e., NR-MS-Ce6) on EMT6 murine mammary carcinoma cells could potentiate the activation of both J774A.1 macrophages and DC2.4 dendritic cells. The activation of these innate immune cells by the conditioned media from cancer cells treated with combined PDT + PTT was cell-type and number dependent. While treated B16-OVA murine melanoma cells induced lower activation levels for both immune cell types compared to EMT6, they caused higher pro-inflammatory cytokine secretion levels. Our study suggests the importance of immunological investigations to complement any nanoparticle-based therapeutic interventions to better evaluate their efficacy. This could be achieved through a simple approach to screen for the first line of immune responses arising from these therapies prior to in vivo studies.

Combinatorial treatment of photothermal therapy using gold nanoshells with conventional photodynamic therapy to improve treatment efficacy: an in vitro study.

BACKGROUND AND OBJECTIVE: Both photodynamic (PDT) and photothermal (PTT) therapy have proven to be effective treatment strategies for cancer, but the approach of combining them into a single treatment modality may offer better treatment efficacy. We compare the treatment efficacy of such combined treatment with the individual treatment. STUDY DESIGN/MATERIALS AND METHODS: We perform the individual PDT, PTT and combined treatment under selected in vitro condition with our low light dose of 1.44 J/cm(2) and compare their cell viability using crystal fast violet assay. RESULTS: Compared to PDT and PTT alone which can reduce cell viability to 30.9% and 44.0% respectively, the combined treatment under a single irradiation can further reduce the cell viability to 17.5%. CONCLUSION: A combined PDT and PTT treatment appears to be a more effective treatment strategy compared to conventional PDT or emerging PTT treatment.