Nanoparticles-based phototherapy systems: molecular mechanisms and clinical applications

Nanoparticle-based phototherapy represents a paradigm shift in precision medicine, harnessing light-activated mechanisms to modulate cellular pathways across a spectrum of diseases. By integrating nanoparticles, phototherapeutic modalities achieve enhanced light absorption and improved targeting and amplification effects, such as reactive oxygen species generation in photodynamic therapy and localized heating in photothermal therapy. Gold nanoparticles and hybrid constructs have attracted considerable attention in both photothermal and photodynamic therapies, while delivery platforms, such as liposomes and dendrimers, fine-tune biodistribution and release kinetics. At the molecular level, phototherapy induces oxidative stress, triggers apoptotic and autophagic cascades and modulates immune responses by altering cytokine profiles and T-cell activity processes, which are critical not only in cancer therapy but also in managing various chronic conditions, including cardiovascular, neurodegenerative, metabolic and autoimmune disorders. In this review, we chart the evolution of nanoparticle-based phototherapy systems by examining their core components, classification schemes and delivery platforms that drive treatment specificity. We then dissect the underlying signaling pathways, highlighting how light-triggered interventions intersect with key molecular networks in chronic disease contexts. Additionally, we critically evaluate FDA-approved agents and insights from recent clinical trials, outlining the major challenges to clinical translation, including nanoparticle optimization, efficient light delivery and regulatory hurdles. By integrating molecular insights with clinical advancements, nanoparticle-based phototherapy has emerged as a transformative, noninvasive strategy poised to revolutionize therapeutic approaches for a wide range of diseases.