Surface Nanopore Engineering of 2D MXenes for Targeted and Synergistic Multitherapies of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and deadly gastrointestinal malignancies. Given its insensitivity to traditional systematic chemotherapy, new therapeutic strategies for efficient HCCs treatment are urgently needed. Here, the development of a novel 2D MXene‐based composite nanoplatform for highly efficient and synergistic chemotherapy and photothermal hyperthermia against HCC is reported. A surface‐nanopore engineering strategy is developed for the MXenes’ surface functionalization, which achieves the uniform coating of a thin mesoporous‐silica layer onto the surface of 2D Ti3C2 MXene (Ti3C2@mMSNs). This strategy endows MXenes with well‐defined mesopores for on‐demand drug release/delivery, enhanced hydrophilicity/dispersity, and abundant surface chemistry for targeting engineering. Systematic in vitro and in vivo evaluations have demonstrated the high active‐targeting capability of arginine‐glycine‐aspartic acid (RGD)‐targeting Ti3C2@mMSNs into tumor, and the synergistic chemotherapy (contributed by the mesoporous shell) and photothermal hyperthermia (contributed by the Ti3C2 MXene core) completely eradicate the tumor without obvious reoccurrence. This work not only provides a novel strategy for efficiently combating HCC by developing MXene‐based composite nanoplatforms, but also paves a new way for extending the biomedical applications of MXenes by surface‐nanopore engineering. Surface nanopore‐engineered 2D MXene‐based composite nanosheets (Ti3C2@mMSNs) are successfully constructed, which consist of a mesoporous‐silica surface for on‐demand chemotherapy and a Ti3C2 MXene core for photothermal hyperthermia. Systematic in vitro and in vivo evaluations demonstrate the high active‐tumor‐targeting capability of the arginine‐glycine‐aspartic acid (RGD)‐targeting Ti3C2@mMSNs, and synergistic chemotherapy and photothermal hyperthermia completely eradicate hepatocellular carcinoma tumors without obvious reoccurrence.