Ti3C2Tx MXene nanosheet-based drug delivery/cascaded enzyme system for combination cancer therapy and anti-inflammation

Photothermal therapy (PTT)-based combination therapy is an effective approach to cancer treatment. However, there is a possibility of tumor development due to the inflammation caused by PTT. In addition, hyperthermia can cause damage to normal tissues. This work reported a drug delivery/cascade enzyme system based on Ti 3 C 2 T x MXene nanosheets. Ultra-small, degradable mesoporous silica nanoparticles (DS-MSN) were prepared to load phloretin (Phl), which has anti-inflammatory, antioxidant, and anticancer properties. Subsequently, glucose oxidase (GOx) was adsorbed on the surface of DS-MSN. The nanoparticles were then modified on Ti 3 C 2 T x MXene nanosheets and finally treated with polyethylene glycol (PEG) to obtain the multifunctional system named Ti 3 C 2 T x -Phl@DS-MSN-GOx-PEG (TPDMGP). The high near-infrared photothermal conversion efficiency of Ti 3 C 2 T x made it suitable for PTT. GOx and Ti 3 C 2 T x formed a cascade enzyme system inside cancer cells: Ti 3 C 2 T x exhibited catalase (CAT)-like activity that decomposed intracellular hydrogen peroxide (H 2 O 2 ) into O 2 , which was provided to GOx for enhanced starvation therapy. GOx in the presence of O 2 produces H 2 O 2 , for the oxygen production of Ti 3 C 2 T x . Meanwhile, DS-MSN could be degraded in the reducing environment inside cancer cells as it contains disulfide bonds in its backbone, thus releasing Phl for chemotherapy. Such a combination therapy strategy could achieve a satisfactory therapeutic outcome by low-temperature PTT while evading normal tissue damage by high temperature. The anti-inflammatory effects of both Ti 3 C 2 T x and Phl enabled TPDMGP to eliminate the inflammation caused by PTT via the scavenging of reactive oxygen species (ROS). The multifunctional system is expected to generate new paradigms for cancer PTT.