Design Strategies and Mechanisms of Nanoconstructs for Photoimmunotherapy in Cancer: A Review

Abstract Although remarkable advances in cancer treatment have led to longer survival, mortality associated with tumors has shown only limited reduction over the past few decades. In recent years, photoimmunotherapy (PIT) has emerged as a promising therapeutic paradigm that integrates thermal ablation and immunotherapy for synergistic antitumor effects. In addition to directly killing tumor cells via thermal ablation, this approach also activates the host immune response. However, poor tumor targeting, off-target release of the therapeutic agent, and non-specific immune effects hinder the clinical translation of PIT. To address these issues, temperature-sensitive “smart” nanocarriers that could selectively release the therapeutic load in a controlled manner have been reported. Among these, those that are responsive to mild hyperthermia have attracted significant attention, as these nanocarriers not only enhance tumor accumulation but also induce immune activation in the tumor microenvironment. Furthermore, PIT involves PDT/PTT-combined immunotherapy, targeted photo-immunoadjuvants, and nanomedicine-based delivery systems that integrate immune checkpoint blockade and cancer vaccines. This review summarises recent progress in temperature-responsive nanoplatforms for PTT-based immunotherapy. These nanoplatforms focus on molecular design, nanoengineering strategies, immune modulation mechanisms, and the potential to overcome therapeutic resistance at both preclinical and clinical levels.