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

Abstract

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 (Nb₂C) Mxene. PT2 was loaded onto the surface of poly(vinylpyrrolidone) (PVP)-coated Nb₂C MXene through electrostatic interaction to obtain Nb₂C-PVP-PT2 nanosheets (NSs) with a high loading efficiency of 153.7%. Nb₂C MXene exhibited catalase-like activity, which could catalyze hydrogen peroxide (H₂O₂) to produce O₂, in turn alleviating tumor hypoxia and enhancing the efficacy of SDT. The depletion of H₂O₂ further results in abnormal cellular H₂O₂ 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.