Harnessing Boron-Mediated Ti Valence Cycling in TiB₂-PEG-DOX: A Multimodal CDT/PTT/CT Platform for Colorectal Cancer...

Titanium-based materials hold great biomedical potential owing to excellent biocompatibility. But titanium diboride (TiB₂), an emerging metal boride, is rarely explored for antitumor use, and developing multifunctional TiB₂-based nanoplatforms with enhanced catalytic activity is urgently needed. Herein, we constructed a nanoplatform (TiB₂-PEG-DOX) by modifying TiB₂ nanosheets (TiB₂ NSs) with amino polyethylene glycol (NH₂-PEG-NH₂) and loading doxorubicin (DOX) via electrostatic interaction. We first clarified the boron (B)-mediated Ti valence cycle: B regulates Ti electron transfer, promotes Ti⁴⁺ reduction to Ti²⁺, enhancing H₂O₂-rich tumor microenvironment Fenton-like reaction to generate cytotoxic •OH for chemodynamic therapy (CDT). Meanwhile, TiB₂-PEG-DOX shows 53.53% photothermal conversion efficiency under 808 nm near-infrared (NIR) irradiation for efficient photothermal therapy (PTT), and NIR further triggers on-demand DOX release. DOX accumulates at tumor sites via the enhanced permeability and retention (EPR) effect to exert chemotherapy (CT). In vitro, it eliminates 86.32% of HCT-116 colorectal cancer cells via CDT/PTT/CT synergy; in vivo, it achieves nearly complete tumor ablation in mice with excellent biocompatibility. This work provides a high-performance synergistic antitumor platform and establishes a B-modulated metal valence cycling paradigm, paving the way for titanium-based nanomedicines.