A Gas/phototheranostic Nanocomposite Integrates NIR‐II‐Peak Absorbing Aza‐BODIPY with Thermal‐Sensitive Nitric Oxide Donor for Atraumatic Osteosarcoma Therapy

Abstract Photothermal therapy (PTT) has received increasing interest in cancer therapeutics owing to its excellent efficacy and controllability. However, there are two major limitations in PTT applications, which are the tissue penetration depth of lasers within the absorption range of photothermal agents and the unavoidable tissue empyrosis induced by high‐energy lasers. Herein, a gas/phototheranostic nanocomposite (NA1020‐NO@PLX) is engineered that integrates the second near‐infrared‐peak (NIR‐II‐peak) absorbing aza‐boron‐dipyrromethenes (aza‐BODIPY,NA1020) with the thermal‐sensitive nitric oxide (NO) donor (S‐nitroso‐N‐acetylpenicillamine, SNAP). An enhanced intramolecular charge transfer mechanism is proposed to achieve the NIR‐II‐peak absorbance (λ_max = 1020 nm) on NA1020, thereby obtaining its deep tissue penetration depth. The NA1020 exhibits a remarkable photothermal conversion, making it feasible for the deep‐tissue orthotopic osteosarcoma therapy and providing favorable NIR‐II emission to precisely pinpoint the tumor for a visible PTT process. The simultaneously investigated atraumatic therapeutic process with an enhanced cell apoptosis mechanism indicates the feasibility of the synergistic NO/low‐temperature PTT for osteosarcoma. Herein, this gas/phototheranostic strategy optimizes the existing PTT to present a repeatable and atraumatic photothermal therapeutic process for deep‐tissue tumors, validating its potential clinical applications.