A Dual-Locked and H2S-NO Tandem-Activatable NIR-II Nanoagent for Colon Cancer Theranostics.

Abstract

Dual-locked activatable theranostics have been emerging as a promising cancer therapy platform. However, most of the reported dual-locked systems only restricted to enzyme-responsive probes, new molecular tools with other biomarker-responsiveness still remain challenging. Moreover, optical manipulation in the second near-infrared (NIR-II) window can potentially boost the theranostic efficacy, but having rarely been explored. In this study, we report a dual-locked and gas tandem-activatable NIR-II nanoagent for colon cancer theranostics. Water-dispersible nanoparticles containing a nitrated organic small molecule (CTBN) and an acid-responsive NO donor (NONOate; CTBNN-NPs) are fabricated, displaying negligible emission in visible-NIR region. Upon uptake by colon cancer cells, CTBNN-NPs can be tandemly activated by the overexpressed H2S and the in situ released NO, thus turning on NIR-II emission extending to 1200 nm. Moreover, the activated CTBNN-NPs also demonstrate augmented NIR absorption as well as robust photothermal and type-I photodynamic performance, achieving NIR-II fluorescence imaging-guided efficient photo-elimination of colon cancer together with NO gas therapy, while exhibiting limited efficacy in the tested cervical and breast cancer models. This work provides a new molecular design approach to dual-locked and H2S-NO tandem-activatable nanoagents with gas-responsive and NIR-II active capabilities, highlighting the exciting potential for cancer theranostics.

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