Light as a Weapon: Redefining Cancer Care with Photodynamic Therapy

Photodynamic therapy (PDT) has evolved over the past decade into a versatile cancer treatment modality, fueled by advances in photosensitizer design, nanotechnology, and immunotherapy. Smarter photosensitizers, ranging from activatable and oxygen-independent scaffolds to red/NIR-absorbing chromophores, have expanded tumor selectivity and tissue penetration. Nanocarrier-based delivery systems have improved solubility, biodistribution, and combinatorial theranostic potential, while innovative light sources such as upconversion nanoparticles, implantable LEDs, and X-ray-driven PDT are addressing penetration constraints. Importantly, PDT is no longer confined to local cytotoxicity but is increasingly recognized as an immunomodulatory platform capable of synergizing with immune checkpoint blockade (ICB) and <i>in situ</i> vaccination strategies. However, despite this progress, significant barriers remain, including poor standardization of dosimetry, heterogeneity in tumor hypoxia, unresolved safety concerns regarding nanocarriers, and limited clinical validation of combination regimens. This highlight review critically evaluates these advances and bottlenecks, outlining how PDT can realistically transition from a niche light-based therapy into a central component of precision oncology and next-generation immunotherapy.