Phase-Transition-Induced Deformable OMV-Camouflaged Nanoparticles Enabling Deep Biofilm Penetration for...

Bacterial pneumonia remains refractory to conventional therapies due to the dense extracellular polymeric substance matrix of biofilms that severely restricts drug penetration. Here, we report a biomimetic, thermo-responsive nanoplatform (AIE/PCM@OMV) featuring phase-transition-induced deformability to overcome biofilm barriers and treat bacterial pneumonia. The nanoparticles comprise a phase-change material (PCM) core encapsulating an aggregation-induced emission (AIE) phototherapeutic agent and are camouflaged with bacterial outer membrane vesicles (OMVs). The OMV coating enables homologous targeting and preferential accumulation within biofilms derived from the parental strain. Upon 660 nm laser irradiation, the AIE agent simultaneously generates localized heat and reactive oxygen species, inducing synergistic photothermal-photodynamic bacterial ablation while triggering a solid-to-liquid transition of the PCM core. This phase transition confers dynamic deformability, allowing adaptive structural transformation and deep penetration into biofilms. AIE/PCM@OMV achieves 99.9% eradication of wild-type Escherichia coli biofilms in vitro and reduces pulmonary bacterial burden by 99% in a murine pneumonia model, alleviating lung edema and restoring alveolar architecture. Mechanistically, the therapy reprograms the immune microenvironment by suppressing excessive inflammatory signaling and promoting M2 macrophage polarization. This work establishes a phase-transition-driven deformable biomimetic nanostrategy that integrates homologous targeting, adaptive penetration, and synergistic photothermal-photodynamic therapy for effective treatment of biofilm-associated bacterial pneumonia.