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 cm⁻²), eliminating off-target toxicity while achieving complete bacterial eradication within 120 min, with 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.