Multidimensional profiling of functionalized photothermal nanoplatforms for synergistic cancer immunotherapy: Design, strategy, and challenge

Currently, photothermal immunotherapy (PTIT) using functionalized photothermal nanoplatforms synergized with immune-related drugs has been shown in numerous studies to be successful in the treatment of primary, recurrent, or metastatic cancers. Generally, hyperthermia driven by near-infrared light can stimulate a certain antitumor immune response by inducing immunogenic cell death while directly ablating tumor cells. However, single photothermal therapy is insufficient to initiate a comprehensive host immune program against tumors, and tumor tissue contains a complex immunosuppressive microenvironment, necessitating the combination of other cooperative therapeutic strategies that can enhance immune response or block immune suppression for increased PTIT efficacy. Given the biological delivery barriers of nanomedicine in PTIT, the reasonable design of nanocarriers from a multidimensional perspective is emphatically discussed here, primarily involving material categories and structural constituents, diverse physicochemical properties, and functional diversity. Furthermore, the impact of exceedingly complex variables in the tumor microenvironment (TME) on PTIT should be considered, such as poor immunogenicity, immunosuppression, hypoxia, and dense extracellular matrix. So, several collaborative strategies to augment tumor infiltration of immune cells and restore tumor immune surveillance are currently summarized, including directly amplified immune responses, reversal of immunosuppressive environments, and remodeling of typical TME features. Finally, the pre-clinical and clinical issues in existing PTIT techniques based on functionalized nanoplatforms are critically criticized, and some potential solutions are given accordingly. In any case, this review aims to offer a series of suitable nanomaterial designs and optimal treatment methodologies for PTIT research, as well as suggest some ideas for future forays into clinical research.