Polymeric nanocarriers for subcellular targeting in photodynamic therapy

Photodynamic therapy (PDT) is a clinically established modality that induces localized cell death through the light activation of a photosensitizer (PS). While celebrated for its exceptional cosmetic outcomes, PDT protocols remain largely empirical, and their efficacy is influenced by complex factors beyond simple photochemical yield. A critical paradigm shift has highlighted that the subcellular localization of the PS is a more decisive factor for cell death efficiency than the total load of reactive species generated. Consequently, targeting PSs to vital organelles like mitochondria, lysosomes, and the endoplasmic reticulum has become a primary focus for improving therapeutic selectivity. This review provides a comprehensive overview of advanced polymeric nanocarriers engineered for this precise subcellular targeting. We examine the role of these nanoplatforms as both protective drug carriers and active targeting agents, emphasizing their advantages in stability, biocompatibility, and modular design. The discussion critically assesses the therapeutic potential and inherent challenges of targeting specific organelles to optimize the efficacy-to-toxicity ratio. The integration of polymer science with photobiology and nanomedicine is presented as a promising frontier for the rational development of superior PDT treatments.