Green-Synthesised Nanoconjugates: Advancing Targeted Photodynamic Therapy for Lung Cancer

Lung cancer is a type of cancer that develops around the airways or lungs and continues to be the leading cause of cancer-related deaths worldwide. This has necessitated the need for innovative therapeutic strategies to overcome the limits of existing therapies such as surgery, chemotherapy and radiotherapy. Photodynamic therapy (PDT) has emerged as a promising non-invasive treatment for lung cancer. This approach utilises photosensitisers (PSs) activated by light to generate reactive oxygen species (ROS), ultimately leading to cancer cell death. However, the effectiveness of PDT is often limited by several factors, including poor delivery of the PSs, low selectivity for cancer cells, and insufficient generation of ROS. This has created a need to further innovate therapeutic strategies to combat these shortfalls. Advancements in nanotechnology have introduced eco-friendly or green-synthesis methods by utilising plant extracts to produce silver nanoparticles (AgNPs). These have enhanced biocompatibility, reduced toxicity and can be used as effective carriers for PSs. Conjugating PS to green-synthesised AgNPs improves drug stability, targeting capabilities, and overall therapeutic outcomes. Furthermore, AgNPs possess intrinsic plasmonic properties that enhance light absorption, thereby increasing ROS generation synergistically with PS activation. Despite all these advances, there remain several challenges, such as long-term biosafety concerns and the scalability of green synthesis. This review discusses the synergistic potential of green-synthesised AgNPs-PS conjugates in improving PDT for lung cancer via targeting lung cancer stem cells while examining their underlying mechanisms, recent preclinical and clinical advancements and future perspectives.