photochemotherapy

Overview

Photochemotherapy, more widely known as photodynamic therapy (PDT), is a minimally invasive therapeutic modality that employs the combined action of a photosensitizing chemical agent, molecular oxygen, and light of a specific wavelength to generate cytotoxic reactive oxygen species (ROS) capable of inducing cell death. The fundamental mechanism relies on the photoexcitation of a photosensitizer — a molecule that absorbs photons and transfers energy to molecular oxygen — producing singlet oxygen and other ROS that damage cellular membranes, organelles such as the mitochondrion, and DNA, ultimately triggering apoptosis or necrosis in target tissues. This mechanism confers a high degree of spatiotemporal controllability, confining cytotoxic activity to illuminated regions and thereby minimizing systemic toxicity relative to conventional chemotherapy or (chemo)radiotherapy.

PDT has established clinical utility across oncology and dermatology, with applications spanning Malignant Disease of the skin, bladder cancer, ovarian cancer, liver cancer, head/neck tumors, breast, colorectal, and prostate tumors, as well as pre-cancerous lesions driven by viral infections such as high-risk human papillomavirus. Beyond oncology, it has found use in infectious disease contexts, including the eradication of bacteria in infected wounds. Its selectivity for abnormal or rapidly proliferating cells, combined with tissue-preserving characteristics, makes it a particularly attractive strategy in settings where organ function must be conserved.

Focus of Latest Publications

Recent publications on photochemotherapy have focused largely on improving photodynamic therapy through combination strategies and engineered nanoplatforms. One study in oral squamous cell carcinoma evaluated whether metformin could potentiate methylene blue-mediated photodynamic therapy in tongue cancer cells in vitro, with the goal of clarifying possible molecular mechanisms. Another report described fluorene-based fluorescent nanoprobes designed for ethanol-responsive cancer diagnosis and photodynamic therapy, using substituent engineering to enhance singlet oxygen generation and fluorescence response. In colon cancer cells, these nanoprobes showed strong ethanol selectivity and, under irradiation, reduced cell viability.

Several reviews and platform studies have emphasized nanomaterial-enabled photochemotherapy in oncology. Titanium dioxide nanoparticles were reviewed as adjuncts that can augment cancer therapies including photodynamic therapy, although the review also highlighted cytotoxicity, genotoxicity, and long-term safety concerns. Plasmonic nanotheranostics were discussed as unified imaging-and-therapy systems that can support plasmon-mediated photochemical processes and synergistic combinations such as photothermal therapy-photodynamic therapy and photothermal therapy-chemotherapy. Similarly, functional organic luminogens were presented as precision theranostic materials that integrate imaging with photodynamic and photothermal treatment, with attention to structure-property relationships, biocompatibility, and translational challenges.

Other recent work has centered on overcoming tumor microenvironment barriers to photochemotherapy. A dual-modal nanoplatform combining glutathione depletion with near-infrared-triggered therapy was developed to amplify photothermal and photodynamic effects; by depleting intracellular glutathione and enhancing oxidative stress, it improved Ce6-based photodynamic therapy and enabled synergistic tumor eradication with photothermal therapy in vitro and in vivo. A review of metal-organic framework-based drug delivery systems likewise highlighted their responsiveness to light and their use in combination with photodynamic therapy, photothermal therapy, chemotherapy, and immunotherapy to modulate the tumor microenvironment. Collectively, these publications portray photochemotherapy as an increasingly multimodal approach, often paired with nanotechnology, redox modulation, or other therapies to improve antitumor efficacy.