NIR Light-Responsive Ti₃C₂ MXenes Mediate Controlled Aqueous Degradation and Highly Efficient Photothermal Conversion for Targeted Cancer Phototherapy

Many cancer types are typically diagnosed in advanced stages and tend to have low survival rates. There are numerous varieties of nanomedicine platforms developed to tackle them. Among them, two-dimensional Ti₃C₂ MXene nanosheets (NSs) have emerged as a versatile platform, owing to their high surface area enriched with various functional groups, near-infrared (NIR) responsiveness, and superior photothermal characteristics. However, they have poor aqueous stabilities and are prone to degradation, which can severely limit their utility in biomedical applications. This leaves a grand challenge to explore Ti₃C₂ MXene NS-based platforms for biomedical applications. Herein, we report the first demonstration of a NIR light-responsive Ti₃C₂ MXene NS-based platform with highly efficient photothermal conversion and controlled degradation in aqueous environments. Additionally, it enables targeted photothermal therapy (PTT) and photodynamic therapy (PDT) to address progressive cancers. The nanoplatform integrates folic acid (<u>F</u>A) moieties, the FDA-approved NIR photosensitizing drug indocyanine green (<u>I</u>CG), curcumin (<u>C</u>ur), and <u>T</u>i₃C₂ MXene NSs (FICT NSs). Upon NIR light activation, the FICT nanoplatform is capable of producing both heat and singlet oxygen (¹O₂) along with the release of the Cur drug to mediate the targeted phototherapy of cancers via inhibiting profound cancer cell migration. Such FICT nanoplatforms also exhibited controlled aqueous degradability, which can greatly enhance their drug release and biocompatibility while minimizing the toxicity. Further, the FICT nanoplatform has demonstrated the targeted photothermal and photodynamic therapeutic capabilities in both in vitro 2D cellular and 3D spheroid models. We foresee that this innovative nanoplatform has considerable potential for future clinical applications.