Advancing Lung Cancer Treatment: A Comprehensive Review of Photodynamic Therapy and Nanoparticle Applications.

Lung cancer remains a significant global health challenge. The high mortality rate is primarily caused by late diagnoses and the limitations of conventional therapies. Photodynamic therapy (PDT), which uses photosensitizing compounds, specific wavelengths of light, and oxygen to generate cytotoxic reactive oxygen species (ROS) that selectively destroy cancer cells, has emerged as a promising, minimally invasive alternative. Despite its advantages, traditional PDT has limitations. These include the limited penetration depth of light and the hypoxic nature of the tumor microenvironment. Nanotechnology has transformed PDT by enabling the precise delivery of photosensitizers, improving their stability, overcoming physiological barriers, and allowing for deeper tissue targeting. This review analyzes the molecular mechanisms of PDT, the evolution of photosensitizer and nanoparticle design, strategies to overcome PDT limitations, and the impact of the tumor microenvironment. Additionally, the potential of combining PDT with other cancer therapies, such as chemotherapy, immunotherapy, targeted therapy, radiotherapy, and gene therapy, is being investigated. While preclinical successes are remarkable, clinical implementation of nanoparticle-based PDT faces complex regulatory pathways, manufacturing scalability challenges, and the need for robust long-term safety data. Integrating artificial intelligence (AI) and biomarker discovery will accelerate the development of personalized treatments and usher in a new era of targeted oncology for lung cancer patients.