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

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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) was engineered that integrated the NIR-II-peak absorbing aza-BODIPY (NA1020) with the thermal-sensitive nitric oxide donor (S-nitroso-N-acetylpenicillamine, SNAP). An enhanced intramolecular charge transfer mechanism was proposed to achieve the NIR-II-peak absorbance (λmax = 1020nm) on NA1020, thereby obtaining its deep tissue penetration depth. The NA1020 exhibited 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 indicated the feasibility of the synergistic NO/low-temperature PTT for osteosarcoma. Herein, this gas/phototheranostic strategy optimized the existing PTT to present a repeatable and atraumatic photothermal therapeutic process for deep-tissue tumors, validating its potential clinical applications. This article is protected by copyright. All rights reserved.