Lung cancer remains one of the most lethal malignancies worldwide, demanding therapeutic strategies that are both effective and minimally invasive. Photodynamic therapy, which relies on the synergistic action of a photosensitizer, light, and molecular oxygen, offers selective tumour destruction with reduced systemic toxicity is used in many medical fields including lung cancer. However, traditional photodynamic therapy suffers from poor photosensitizer solubility, limited tumour penetration, and hypoxia-driven treatment resistance. Recent advancements in nanotechnology have led to the development of novel photosensitizers and delivery systems that improve solubility, stability, and tumor-specific accumulation. Nanomedicine provides a transformative solution by enhancing photosensitizer delivery, photostability, subcellular targeting, and intratumoral distribution. Different nanocarrier systems improve PDT efficacy through distinct mechanisms. Liposomes enhance biocompatibility and enable preferential tumour accumulation of hydrophobic photosensitizers. Polymeric nanoparticles and dendrimers provide controlled release, improved intracellular trafficking, and organelle-specific targeting, thereby amplifying apoptosis and autophagy pathways. Inorganic nanostructures, such as bismuthene nanosheets and iron-oxide platforms, contribute unique optical and catalytic properties, supporting ROS amplification, oxygen modulation, and imaging-guided photodynamic therapy. This review includes the pathophysiology of lung cancer, mechanistic foundations of photodynamic therapy, nanocarrier-based advances, associated patents,recent clinical trials and emerging combinatorial strategies integrating chemotherapy, radiotherapy, gene therapy, and immunotherapy. Current limitations—such as restricted light penetration, tumour hypoxia, and translational challenges—are critically evaluated alongside future directions involving artificial intelligence-driven nanocarrier design. Collectively, nanotechnology-integrated photodynamic therapy represents a promising, evolving platform for overcoming therapeutic barriers and improving clinical outcomes in lung cancer. • Nanocarriers enhance photosensitizer delivery and overcome PDT limitations. • Lipid, polymeric, and inorganic nanosystems boost ROS and tumour targeting. • Nano-PDT improves solubility, photostability, and subcellular localisation. • Combination nano-PDT activates strong immunogenic and apoptotic pathways. • Clinical trials highlight growing potential of nano-enabled PDT systems.
Mishra et al. (Wed,) studied this question.