A dual stimulus-responsive NIR-II photoacoustic probe for precise diagnosis of colon cancer and photothermal-starvation synergistic therapy

Integrating imaging-guided diagnoses with therapeutic strategies holds significant potential in the treatment of cancer and other diseases. Herein, we developed a dual stimulus-responsive nanoagent that is responsive to two specific stimuli, and demonstrated its application to the diagnosis and photothermal-starvation therapy of colon cancer. The elevated levels of H2S and glucose in colon cancer cells are used as targets for a dual stimulus- responsive, self-assembled copper-albumin-glucose oxidase@polyaniline (Cu2 +-BSA-GO x @PANI) nanoplatform. Upon entering colon cancer cells, GOx oxidizes glucose to produce gluconic acid, which leads to the protonation of PANI and the red-shifting of the wavelength of maximum absorbance of the nano-platform from 680 nm to 780 nm. Concurrently, Cu2+ reacts with H2S to form CuS, which further induces a redshift from 780 nm to 830 nm, and significantly enhancing the near-infrared II region absorption intensity and enabling photoacoustic imaging under 1064 nm laser irradiation. Additionally, the consumption of glucose within cancer cells inhibits the generation of ATP, achieving starvation therapy while reducing the expression of tumor heat- shock protein 90 to weaken tumoral thermo-tolerance, resulting in a synergistic anti-tumor effect. In vitro and in vivo analyses indicate that the Cu2+-BSA-GOx@PANI nano-platform possesses specific visual diagnostic and therapeutic capabilities for colon cancer, providing a novel strategy for the design of highly effective nanodiagnosis-treatment agents.