Photothermal therapy (PTT) has attracted extensive research attention as a noninvasive and selective treatment strategy for numerous cancers. PTT functions via photothermal effects induced by converting light energy into heat on near-infrared laser irradiation. Despite the great advances in PTT for cancer treatment, the photothermal therapeutics using laser devise only or non-specific small molecule PTT agents has been limited because of its low photothermal conversion efficiency, concerns about the biosafety of the photothermal agents, their low tumor accumulation, and a heat resistance of specific types of cancer. Using nanomaterials as PTT agents themselves, or for delivery of PTT agents, offers improved therapeutic outcomes with fewer side effects through enhanced photothermal conversion efficiency, accumulation of the PTT agent in the tumor tissue, and, by extension, through combination with other therapies. Herein, we review PTT’s current clinical progress and present the future outlooks for clinical applications. To better understand clinical PTT applications, we describe nanomaterial-mediated photothermal effects and their mechanism of action in the tumor microenvironment. This review also summarizes recent studies of PTT alone or in combination with other therapies. Overall, innovative and strategically designed PTT platforms are promising next-generation noninvasive cancer treatments to move closer toward clinical applications.

Mesoporous silica nanoparticles (MSNs) with stimuli-responsive gatekeepers have been extensively investigated for controlled drug delivery at the target sites. Herein, we developed reactive oxygen species (ROS)-responsive MSNs (R-MSNs), consisting of a gadolinium (Gd)–DOTA complex as the ROS-responsive gatekeeper and polyethylene glycol (PEG)-conjugated chlorin e6 as the ROS generator, for magnetic resonance (MR) imaging-guided photodynamic chemotherapy. Doxorubicin (DOX), chosen as an anticancer drug, was physically encapsulated into DOTA-conjugated MSNs, followed by chemical crosslinking via the addition of GdCl₃. DOX-R-MSNs could effectively maintain their structural integrity in a physiological environment for 7 days and show an enhanced in vitro T₁-MR imaging signal for the Gd–DOTA complex. Upon 660 nm laser irradiation, the release rate of DOX from DOX-R-MSNs remarkably increased along with the disintegration of the gatekeeper, whereas DOX release was significantly retarded without irradiation. When DOX-R-MSNs were intravenously injected into tumor-bearing mice, they were effectively accumulated in tumor tissue, which was demonstrated using MR imaging. In addition, tumor growth was significantly suppressed by DOX-R-MSNs, allowing for site-specific release of DOX in a photodynamically maneuvered manner. Overall, these results suggest that R-MSNs have potential as drug carriers for MR imaging-guided photodynamic chemotherapy.