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

Unlabelled: 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 SiO 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 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-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: [Image: see text]

Supplementary Information: The online version contains supplementary material available at 10.1186/s12951-025-03628-z.