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<p>Two-dimensional<?tk 3?> (2D) MXenes are promising theranostic nanoplatforms, but their limited drug-loading capacity and intracellular delivery hinder therapeutic efficacy. Here, we develop a spikey MXene (sMXene) nanosheet via a self-assembly strategy that enables the controlled growth of porous SiO<sub>2</sub> on the MXene surface. Bis [3-(triethoxysilyl) propyl] tetrasulfide was also introduced into the reaction system to achieve the degradation of spikey MXene (dsMXene). The spikey SiO<sub>2</sub> layer enhances drug loading and cellular uptake, while glutathione (GSH)-responsive biodegradability ensures targeted drug release. Leveraging the intrinsic photothermal properties of MXenes, dsMXenes enable combined photothermal-chemotherapy for precise tumor treatment. This study demonstrates the first application of spikey SiO<sub>2</sub>-coated MXene in osteosarcoma therapy, addressing drug resistance caused by exocytosis. Mimicking viral surface topography, dsMXene enhances intracellular drug delivery and enables tumor-specific, GSH-triggered release, overcoming chemoresistance. When loaded with doxorubicin, dsMXene has potent antiosteosarcoma effects both in vitro and in vivo, with minimal off-target toxicity. This innovative integration of spikey surface engineering and stimuli-responsive drug delivery introduces a transformative platform for future cancer therapies, broadening the scope of MXene-based biomedical applications.<?tk 0?></p> Graphic Abstract <p></p>

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Spikey biodegradable MXene nanosheets with enhanced cellular internalization and stimuli-responsive drug delivery for synergistic cancer therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月11日

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  • Tiankun Hui,
  • Chen Wang,
  • Chenchen Fu,
  • Zhen Song,
  • Qikun Zhang,
  • Bingxin Zheng,
  • Jianye Fu,
  • Meng Qiu,
  • Bin Yue

摘要

Two-dimensional (2D) MXenes are promising theranostic nanoplatforms, but their limited drug-loading capacity and intracellular delivery hinder therapeutic efficacy. Here, we develop a spikey MXene (sMXene) nanosheet via a self-assembly strategy that enables the controlled growth of porous SiO2 on the MXene surface. Bis [3-(triethoxysilyl) propyl] tetrasulfide was also introduced into the reaction system to achieve the degradation of spikey MXene (dsMXene). The spikey SiO2 layer enhances drug loading and cellular uptake, while glutathione (GSH)-responsive biodegradability ensures targeted drug release. Leveraging the intrinsic photothermal properties of MXenes, dsMXenes enable combined photothermal-chemotherapy for precise tumor treatment. This study demonstrates the first application of spikey SiO2-coated MXene in osteosarcoma therapy, addressing drug resistance caused by exocytosis. Mimicking viral surface topography, dsMXene enhances intracellular drug delivery and enables tumor-specific, GSH-triggered release, overcoming chemoresistance. When loaded with doxorubicin, dsMXene has potent antiosteosarcoma effects both in vitro and in vivo, with minimal off-target toxicity. This innovative integration of spikey surface engineering and stimuli-responsive drug delivery introduces a transformative platform for future cancer therapies, broadening the scope of MXene-based biomedical applications.

Graphic Abstract