How Did Conventional Nanoparticle-Mediated Photothermal Therapy Become “Hot” in Combination with Cancer Immunotherapy?

SIMPLE SUMMARY: Photothermal therapy (PTT) has become effective through the development of nanoparticle-based photoabsorbers with various functions, such as targeting properties, high light-to-heat conversion, and photostability. Conventional nanoparticle-mediated PTT has attained localized efficiency in cancer treatment by heat-induced apoptosis or necrosis of cancer cells. Currently, such treatment methods evolve into cancer immunotherapy through the induction of immunogenic cell death (ICD). Damage-associated molecular patterns from dead cells by nanoparticle-mediated PTT activate immune cells for systemic anti-cancer effect. In this review, we investigate various nanoparticle-based PTT and compare its methodology to clarify how it undergoes a transition from thermotherapy to immunotherapy. ABSTRACT: One of the promising cancer treatment methods is photothermal therapy (PTT), which has achieved good therapeutic efficiency through nanoparticle-based photoabsorbers. Because of the various functions of nanoparticles, such as targeting properties, high light-to-heat conversion, and photostability, nanoparticle-mediated PTT successfully induces photothermal damage in tumor tissues with minimal side effects on surrounding healthy tissues. The therapeutic efficacy of PTT originates from cell membrane disruption, protein denaturation, and DNA damage by light-induced heat, but these biological impacts only influence localized tumor areas. This conventional nanoparticle-mediated PTT still attracts attention as a novel cancer immunotherapy, because PTT causes immune responses against cancer. PTT-induced immunogenic cell death activates immune cells for systemic anti-cancer effect. Additionally, the excellent compatibility of PTT with other treatment methods (e.g., chemotherapy and immune checkpoint blockade therapy) reinforces the therapeutic efficacy of PTT as combined immunotherapy. In this review, we investigate various PTT agents of nanoparticles and compare their applications to reveal how nanoparticle-mediated PTT undergoes a transition from thermotherapy to immunotherapy.