Harnessing Boron‐Mediated Ti Valence Cycling in TiB ₂ ‐PEG‐DOX: A Multimodal CDT/PTT/CT Platform for Colorectal Cancer Therapy

ABSTRACT Titanium‐based materials hold great biomedical potential owing to excellent biocompatibility. But titanium diboride (TiB 2 ), an emerging metal boride, is rarely explored for antitumor use, and developing multifunctional TiB 2 ‐based nanoplatforms with enhanced catalytic activity is urgently needed. Herein, we constructed a nanoplatform (TiB 2 ‐PEG‐DOX) by modifying TiB 2 nanosheets (TiB 2 NSs) with amino polyethylene glycol (NH 2 ‐PEG‐NH 2 ) and loading doxorubicin (DOX) via electrostatic interaction. We first clarified the boron (B)‐mediated Ti valence cycle: B regulates Ti electron transfer, promotes Ti 4+ reduction to Ti 2+ , enhancing H 2 O 2 ‐rich tumor microenvironment Fenton‐like reaction to generate cytotoxic •OH for chemodynamic therapy (CDT). Meanwhile, TiB 2 ‐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.