Monodisperse, ultrasmall (<5 nm) Cu(2-x)S nanodots (u-Cu(2-x)S NDs) with significantly strong near-infrared absorption and conversion are successfully demonstrated for effective deep-tissue photoacoustic imaging-guided photothermal therapy both in vitro and in vivo. Owing to ultrasmall nanoparticle size and high water dispersibility as well as long stability, such nanodots possess a prolonged circulation in blood and good passive accumulation within tumors through the enhanced permeability and retention effect. These u-Cu(2-x)S NDs have negligible side effects to both blood and normal tissues according to in vivo toxicity evaluations for up to 3 months, showing excellent hemo/histocompatibility. Furthermore, these u-Cu(2-x)S NDs can be thoroughly cleared through feces and urine within 5 days, showing high biosafety for further potential clinical translation. This novel photoacoustic imaging-guided photothermal therapy based on u-Cu(2-x)S NDs composed of a single component shows great prospects as a multifunctional nanoplatform with integration and multifunction for cancer diagnosis and therapy.

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Noninvasive and targeted physical treatment is still desirable especially for those cancerous patients. Herein, we develop a new physical treatment protocol by employing CO2 bubbling-based 'nanobomb' system consisting of low-intensity ultrasound (1.0 W/cm2) and a well-constructed pH/temperature dual-responsive CO2 release system. Depending on the temperature elevation caused by exogenous low-intensity therapeutic ultrasound irradiation and the low pH caused by the endogenous acidic-environment around/within tumor, dual-responsive CO2 release system can quickly release CO2 bubbles, and afterwards, the generated CO2 bubbles waves will timely explode before dissolution due to triggering by therapeutic ultrasound waves. Related bio-effects (e.g., cavitation, mechanical, shock waves, etc) caused by CO2 bubbles' explosion effectively induce instant necrosis of panc-1 cells and blood vessel destruction within panc-1 tumor, and consequently inhibit the growth of panc-1 solid tumor, simultaneously minimizing the side effects to normal organs. This new physiotherapy employing CO2 bubbling-based 'nanobomb' system promises significant potentials in targetedly suppressing tumors, especially for those highly deadly cancers.