Nanocarrier-mediated photothermal therapy and its combined strategies: mechanism exploration and application in tumour treatment
Zhenni ChenLiu, Chen Gu, Leihan Wang, Qihang Wu, Dong Tang
Abstract
Photothermal therapy (PTT) employs photothermal agents (PTAs) to absorb near-infrared (NIR) radiation and convert it into localized hyperthermia, thereby directly ablating tumor cells and inducing immunogenic cell death (ICD). This process facilitates the release of tumor-associated antigens and damage-associated molecular patterns, eliciting systemic antitumor immunity. Concurrently, PTT remodels the tumor microenvironment by modulating tumor perfusion, vascular architecture, and extracellular matrix permeability. The efficacy of PTT critically depends on the performance of PTAs. To enhance selective heating of malignant cells, targeted photothermal agents—particularly nanoparticles (NPs)—are widely utilized. Nanomaterials serve as a pivotal "bridge" connecting PTT with immunotherapy: PTT generates an in situ antigen reservoir, while nanomaterials function as immune amplifiers. Together, they convert immunologically "cold" tumors into "hot" ones, enabling precise combinatorial cancer immunotherapy. Driven by continuous advances in nanotechnology, photothermal immunotherapy has achieved simultaneous improvements in delivery efficiency and energy conversion precision, substantially accelerating its clinical translation for solid tumors. Representative nanoplatforms—such as gold nanorods, carbon nanotubes, and manganese dioxide nanoshells—not only exhibit high photothermal conversion efficacy but also allow programmable surface conjugation with immune agonists or oxygen-catalyzing modules. These integrated systems alleviate tumor hypoxia and mitigate stromal barriers while enabling in situ presentation of neoantigens derived from thermal damage. Thereby, a single formulation cascades the triple functions of thermal ablation, adjuvant delivery, and in situ vaccination. In this review, we elucidate the mechanistic foundations of PTT in oncology, survey recent developments in phototransductive agents, and discuss innovative strategies and persistent challenges in augmenting PTT efficacy.