Immuno-photodynamic Therapy (IPDT): Organic Photosensitizers and Their Application in Cancer Ablation

Abstract

Photosensitizer-based photodynamic therapy (PDT) has been considered as a promising modality for fighting diverse types of cancers. PDT directly inhibits local tumors by a minimally invasive strategy, but it seems to be incapable of achieving complete eradication and fails to prevent metastasis and recurrence. Recently, increasing events proved that PDT was associated with immunotherapy by triggering immunogenic cell death (ICD). Upon a specific wavelength of light irradiation, the photosensitizers will turn the surrounding oxygen molecules into cytotoxic reactive oxygen species (ROS) for killing the cancer cells. Simultaneously, the dying tumor cells release tumor-associated antigens, which could improve immunogenicity to activate immune cells. However, the progressively enhanced immunity is typically limited by the intrinsic immunosuppressive tumor microenvironment (TME). To overcome this obstacle, immuno-photodynamic therapy (IPDT) has come to be one of the most beneficial strategies, which takes advantage of PDT to stimulate the immune response and unite immunotherapy for inducing immune-OFF tumors to immune-ON ones, to achieve systemic immune response and prevent cancer recurrence. In this Perspective, we provide a review of recent advances in organic photosensitizer-based IPDT. The general process of immune responses triggered by photosensitizers (PSs) and how to enhance the antitumor immune pathway by modifying the chemical structure or conjugating with a targeting component was discussed. In addition, future perspectives and challenges associated with IPDT strategies are also discussed. We hope this Perspective could inspire more innovative ideas and provide executable strategies for future developments in the war against cancer.

Development of Ruthenium Nanophotocages with Red or Near‐Infrared Light‐Responsiveness

“…Photodynamic therapy (PDT) has been widely used in tumor treatment [1] . However, its effectiveness is often constrained by the hypoxic microenvironment and drug resistance exhibited by tumors [2] . To address these problems, the development of photocages or light‐controlled molecular release systems has become one of the research hotspots.…”

“…[1] However, its effectiveness is often constrained by the hypoxic microenvironment and drug resistance exhibited by tumors. [2] To address these problems, the development of photocages or light-controlled molecular release systems has become one of the research hotspots. These systems hold promise as they enable noninvasive and remote regulation of biological systems through light irradiation and photoresponsive molecules.…”

Intranasal mRNA Delivery via Customized RNA-Polyplex Nanoparticles Enhancing Gene Expression through Photochemical Mechanisms

“…In nanoparticle-based gene delivery, the endosomal escape strategy is a key consideration for increasing gene expression efficiency through intracellular internalization. , Since endosome escape after intracellular entry is essential for mRNA expression, an appropriate endosome escape strategy can play a decisive role in the mRNA delivery efficiency of nanoparticles. , Photochemical internalization (PCI) technology can destabilize the endosome membrane by generating reactive oxygen species (ROS) in response to the light of a specific wavelength, making it an effective strategy for gene delivery into the cytoplasm. , Moreover, PCI effect-induced gene internalization works intracellularly and increases the tissue permeability of nanoparticles, even nasal mucosa. , After irradiation with a laser, immune response increases in the in vivo environment due to ROS generated by a photosensitizer. In particular, when the photosensitizer is administered intranasally and then irradiated laser, the T cell immune response increases, causing the photochemical effect, making it possible to apply it to virus treatment and vaccines. , Therefore, the nanoparticles can more effectively penetrate the mucosal layer of the nasal cavity and efficiently deliver mRNA to APCs in nasally associated lymphoid tissue.…”

“…In particular, when the photosensitizer is administered intranasally and then irradiated laser, the T cell immune response increases, causing the photochemical effect, making it possible to apply it to virus treatment and vaccines. 28,29 Therefore, the nanoparticles can more effectively penetrate the mucosal layer of the nasal cavity and efficiently deliver mRNA to APCs in nasally associated lymphoid tissue.…”

Photodynamic Therapy: An Innovative and Versatile Treatment Modality Triggered by Light

“…As a result, considerable efforts have been devoted to circumventing these challenges, making PDT a hot research topic across various disciplines. Recently, the study has been extended to immuno‐PDT, which is a highly promising strategy that can induce systemic immune response to prevent cancer metastasis and recurrence [8] . Various photosensitizers and functional components are being examined and integrated to control the cell‐death pathways and optimize the efficacy in inducing immunogenic cell death.…”