Design and Functionalization of the NIR-Responsive Photothermal Semiconductor Nanomaterials for Cancer Theranostics

Despite the development of medical technology, cancer still remains a great threat to the survival of people all over the world. Photothermal therapy (PTT) is a minimally invasive method for selective photothermal ablation of cancer cells without damages to normal cells. Recently, copper chalcogenide semiconductors have emerged as a promising photothermal agent attributed to strong absorbance in the near-infrared (NIR) region and high photothermal conversion efficiency. An earlier study witnessed a rapid increase in their development for cancer therapy, including CuS, Cu_2-xSe and CuTe nanocrystals. However, a barrier is that the minimum laser power intensity for effective PTT is still significantly higher than the conservative limit for human skin exposure. Improving the photothermal conversion efficiency and reducing the laser power density has become a direction for the development of PTT. Furthermore, in an effort to improve the therapeutic efficacy, many multimode therapeutic nanostuctures have been formulated by integrating the photothermal agents with antitumor drugs, photosensitizers, or radiosensitizers, resulting in a synergistic effect. Various functional materials also have been absorbed, attached, encapsulated, or coated on the photothermal nanostructures, including fluorescence, computed tomography, magnetic resonance imaging, realizing cancer diagnosis, tumor location, site-specific therapy, and evaluation of therapeutic responses via incorporation of diagnosis and treatment. In this Account, we present an overview of the NIR-responsive photothermal semiconductor nanomaterials for cancer theranostics with a focus on their design and functionalization based on our own work. Our group has developed a series of chalcogenides with greatly improved NIR photoabsorption as photothermal agents, allowing laser exposure within regulatory limits. We also investigated the photothermal bioapplications of hypotoxic oxides including WO_3-x, MoO_3-x, and RuO₂, expanding their applications into a new field of photothermal materials. Furthermore, considering a much more enhanced therapeutic effect of multifunctional nanoagents, our group elaborately designed many nanocomposites, such as core-shell nanoparticles of Fe₃O₄@Cu_2-xS and Cu₉S₅@mSiO₂, based on the integration of photothermal agents with contrast agents or other anticancer medicines, achieving cancer theranostic and synergistic treatment. Ternary compound nanocrystals were also prepared with synthetic simplicity for multimodal imaging-guided therapy for cancer. This Account summarizes our past work, including the design and concept, synthesis, and characterization for in vitro and in vivo applications. Then, we analyzed the tendencies of the NIR-responsive photothermal semiconductor nanomaterials for clinical applications, highlighting their prospects and challenges. We believe that the photothermal technology from the NIR-responsive photothermal semiconductor nanomaterials would promote cancer theranostics to result in giant strides forward in the future.