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.

中文翻译：

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2D MXenes的表面纳米孔工程用于肝细胞癌的靶向和协同多药治疗。

肝细胞癌（HCC）是最常见和致命的胃肠道恶性肿瘤之一。由于它对传统的系统化学疗法不敏感，因此迫切需要有效的HCC治疗新的治疗策略。在此，据报道开发了一种新型的基于2D MXene的复合纳米平台，用于高效，协同化学疗法和针对HCC的光热疗。为MXenes的表面功能化开发了一种表面纳米孔工程策略，该策略可在2D Ti ₃ C ₂ MXene（Ti ₃ C ₂@mMSNs）。该策略赋予MXenes良好的中孔，用于按需释放/递送药物，增强的亲水性/分散性以及丰富的表面化学，可用于靶向工程。系统的体外和体内评估表明，精氨酸-甘氨酸-天冬氨酸（RGD）靶向肿瘤的Ti ₃ C ₂ @mMSNs具有很高的主动靶向能力，以及协同化学疗法（由中孔壳贡献）和光热疗（由Ti ₃ C ₂贡献MXene核心）可完全根除肿瘤，而不会再次复发。这项工作不仅提供了通过开发基于MXene的复合纳米平台有效对抗HCC的新颖策略，而且为通过表面纳米孔工程扩展MXene的生物医学应用铺平了新途径。