Catalase-like pleated niobium carbide MXene loaded with polythiophene for oxygenated sonodynamic therapy in solid tumor

Sonodynamic therapy (SDT), an emerging treatment for solid tumors, has the advantages of deep tissue penetration, non-invasiveness, low side effects, and negligible drug resistance. However, the hypoxic environment of deep solid tumors can discount the efficacy of oxygenated dependent SDT. Here, we synthesized a polythiophene-based sonosensitizer ( PT2 ) and a two-dimensional pleated niobium carbide ( Nb 2 C ) Mxene. PT2 was loaded onto the surface of poly(vinylpyrrolidone) (PVP)-coated Nb 2 C MXene through electrostatic interaction to obtain Nb 2 C-PVP-PT2 nanosheets (NSs) with a high loading efficiency of 153.7%. Nb 2 C MXene exhibited catalase-like activity, which could catalyze hydrogen peroxide (H 2 O 2 ) to produce O 2 , in turn alleviating tumor hypoxia and enhancing the efficacy of SDT. The depletion of H 2 O 2 further results in abnormal cellular H 2 O 2 levels and reduced tumor cell activity. Moreover, the decomposed NSs led to the release of the sonosensitizer PT2 that can efficiently generate both singlet oxygen and superoxide anions under ultrasound irradiation. These events led to the inhibition of DNA replication of tumor cells, causing tumor cell death, allowing for enhanced SDT efficacy. Nb 2 C-PVP-PT2 NSs were used for fluorescence imaging-guided enhanced sonodynamic treatment of hypoxic solid tumors by catalytic H 2 O 2 .