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Light-activated photoacoustic imaging (PAI) and photothermal therapy (PTT) using the second near-infrared biowindow (NIR-II, 1000-1350 nm) hold great promise for efficient tumor detection and diagnostic imaging-guided photonic nanomedicine. In this work, we report on the construction of titanium nitride (TiN) nanoparticles, with a high photothermal-conversion efficiency and desirable biocompatibility, as an alternative theranostic agent for NIR-II laser-excited photoacoustic (PA) imaging-guided photothermal tumor hyperthermia. Working within the NIR-II biowindow provides a larger maximum permissible exposure (MPE) and desirable penetration depth of the light, which then allows detection of the tumor to the full extent using PA imaging and complete tumor ablation using photothermal ablation, especially in deeper regions. After further surface polyvinyl-pyrrolidone (PVP) modification, the TiN-PVP photothermal nanoagents exhibited a high photothermal conversion efficiency of 22.8% in the NIR-II biowindow, and we further verified their high penetration depth using the NIR-II biowindow and their corresponding therapeutic effect on the viability of tumor cells in vitro. Furthermore, these TiN-PVP nanoparticles were developed as a contrast agent for NIR-II-activated PA imaging both in vitro and in vivo for the first time and realized efficient photothermal ablation of the tumor in vivo within both the NIR-I and NIR-II biowindows. This work not only provides a paradigm for TiN-PVP photothermal nanoagents working in the NIR-II biowindow both in vitro and in vivo, but also proves the feasibility of PAI and PTT cancer theranostics using NIR-II laser excitation.

Photothermal therapy (PTT) is an emerging technology as a noninvasive therapeutic modality for inducing photonic cancer hyperthermia. However, current photothermal conversion agents suffer from low therapeutic efficiency and single functionality. Engineering crystal defects on the surface or substrate of semiconductors can substantially enhance their optical absorption capability as well as improve their photothermal effects in theranostic nanomedicines. In this study, a specific defect engineering strategy was developed to endow two-dimensional (2D) BiOCl nanosheets with intriguing photothermal conversion performance by creating oxygen vacancies on the surface (O-BiOCl). Importantly, the photothermal performance and photoacoustic imaging capability of the 2D O-BiOCl nanosheets could be precisely controlled by modulating the amounts of oxygen vacancies. The strong Bi-based X-ray attenuation coefficient endowed these nanosheets with the contrast-enhanced computed tomography imaging capability. The high near-infrared-triggered photonic hyperthermia for tumor ablation was systematically demonstrated both in vitro at the cellular level and in vivo for tumor breast cancer mice xenograft models. Based on the demonstrated high biocompatibility of these 2D O-BiOCl nanosheets, this work not only formulates an intriguing 2D photothermal nanoagent for tumor ablation, but also provides an efficient strategy to control the photothermal performance of nanoagents by defect engineering.