Nanomedicine carrier-based combined antitumor strategy integrating phototherapy and immunotherapy

INTRODUCTION: The combination of phototherapy (PTT/PDT) and immunotherapy holds promise for cancer treatment but is hindered by poor spatiotemporal coordination and inadequate targeted co-delivery. Nanomedicine carriers offer a platform to overcome these barriers by enabling precise control over drug release kinetics and reducing off-target toxicity. Methods This review systematically analyzes the rationale, mechanisms, and recent advances in nanocarrier-mediated phototherapy-immunotherapy combination strategies, with a focus on studies published within the last three years. We examine how nanocarriers enable targeted co-delivery, stimuli-responsive release, and enhanced tumor accumulation of phototherapeutic agents and immunomodulators. RESULTS: Phototherapy induces immunogenic cell death (ICD) characterized by calreticulin exposure, ATP secretion, and high-mobility group box 1 (HMGB1) release, which primes dendritic cells and initiates adaptive immunity. Nanocarriers facilitate precise spatiotemporal orchestration of these signals and enable co-delivery with immune checkpoint inhibitors, in situ vaccines, immunomodulators, and adoptive cell therapies, including chimeric antigen receptor (CAR)-T cells. Key outcomes include conversion of "cold" to "hot" tumors, enhanced T-cell infiltration, abscopal effects, and durable immune memory in preclinical models. Emerging trends include multi-responsive nanoplatforms, biomimetic designs, and hypoxia-overcoming strategies that restore antitumor immunity. DISCUSSION: Despite compelling preclinical success, challenges remain in clinical translation, including manufacturing scalability, human tumor heterogeneity, and optimal treatment sequencing. Future directions point towards personalized nanoplatforms, multimodal synergy, and the integration of artificial intelligence and synthetic biology. In conclusion, nanocarrier-mediated phototherapy-immunotherapy integration offers a powerful and evolving approach to achieve durable antitumor immunity and holds transformative potential for solid tumor treatment.