Engineering upconversion nanoparticles for synergistic photodynamic, photothermal and chemotherapy

Cancer remains a significant threat to human health, and photodynamic therapy (PDT) is recognized as a clinically effective therapeutic strategy for tumor treatment owing to its high spatiotemporal control and minimal invasiveness. However, its application is constrained by critical limitations of conventional photosensitizers (PSs), such as narrow excitation wavelength ranges and limited tissue penetration depths. Recently, upconversion nanoparticles (UCNPs) have emerged as a promising strategy to overcome these limitations due to their distinctive near-infrared (NIR) to visible upconverting properties. In particular, the synergistic interaction between UCNPs and PSs has substantially improved the generation efficiency of singlet oxygen (¹O₂), underscoring the therapeutic potential of PDT in managing solid tumors. In this review, we comprehensively discuss the recent advancements in UCNP-based nanoplatforms for synergistic cancer therapy, focusing on the integration of PDT with photothermal therapy (PTT) and chemotherapy. We systematically examined the critical optimization strategies-from rational synthesis and surface functionalization for enhanced biocompatibility and tumor targeting to the design of intelligent nanocarriers for controlled drug release. We also discuss the current challenges facing their clinical translation and highlight prospects in developing integrated theranostic agents for personalized medicine. This review elucidates how these multimodal systems overcome the limitations of monotherapy and would greatly contribute to the research of synergistic photodynamic, photothermal and chemotherapy in the future.