Design of TPGS-functionalized CuBiS nanocrystals with strong absorption in the second near-infrared window for radiation therapy enhancement.

Integrating radiation therapy with high-depth photothermal therapy in the second near-infrared (NIR) window is highly required for efficient treatment of deep-seated tumor cells. Here, we constructed a multifunctional nano-theranostic with bimetallic chalcogenide nanocrystals (NCs) functionalized with amphiphilic d-α-tocopherol polyethylene glycol 1000 succinate (TPGS-CuBiS). Benefiting from the strong absorbance of both X-ray and NIR light in the second NIR window, TPGS-CuBiS CNs can not only deposit more radiation dose to trigger enhanced radiation damage in vivo, but also conduct photo-induced hyperthermia for thermal ablation in the second NIR window and effective improvement of tumor oxygenation to overcome the hypoxia-associated radio-resistance of tumors. Moreover, copper ions on the surface of TPGS-CuBiS NCs are capable of catalyzing the Fenton-like and Haber-Weiss reactions to produce highly reactive hydroxyl radicals, leading to the increase in the level of oxygen radicals and further enhance cancer cell destruction. Apart from their therapeutic application, by means of X-ray computer tomography imaging as well as multispectral optoacoustic tomography imaging, TPGS-CuBiS NCs also have the potential as a nano-theranostic to offer remarkable therapeutic outcome for deep-seated tumor cells in imaging-guided synergistically enhanced radiation therapy.