Lipopolysaccharide-Imprinted Magneto-TiO2 Nanoagents Harness Dopamine Charge Transfer to Drive Visible-Light Photodynamic Therapy for Sepsis

Abstract

Conventional TiO2-based photodynamic therapy (PDT), which relies on ultraviolet (UV) activation, faces critical limitations including non-specific reactive oxygen species (ROS) generation causing collateral tissue damage, high-power density requirements risking thermal injury, and limited spatiotemporal precision due to broad-spectrum absorption. To address these challenges, we constructed a visible-light-driven nanoplatform through ligand-to-metal charge transfer (LMCT) engineering. The platform, termed LPS-MIP, integrates a polydopamine (PDA) molecular imprinting layer with a Fe3O4@SiO2@TiO2 core. The PDA layer not only creates pathogen-specific recognition cavities via boronate affinity imprinting for selective P. aeruginosa binding but also establishes an LMCT pathway with TiO2, shifting its activation spectrum to visible light. This innovation enables UV-free ROS generation under low-intensity white LED light (100 mW/cm2), eliminating off-target toxicity while achieving complete bacterial eradication within 120 min, 6.6-fold higher photocurrent density than UV-activated TiO2. In murine sepsis models, LPS-MIP demonstrated >99% bacterial clearance in the bloodstream, suppressed hyperinflammation (TNF-α/IL-6 reduced to baseline levels), and prevented multiorgan damage, outperforming gentamicin-treated controls. The embedded Fe3O4 core enabled rapid magnetic retrieval, reducing hepatic nanoparticle retention by 85%. By replacing UV with biocompatible visible light and confining ROS production to pathogen-binding sites, this design resolves the long-standing trade-off between antimicrobial efficacy and systemic toxicity, offering a clinically adaptable strategy for precision sepsis therapy.