A Protein-Imprinted Polymer Encapsulates Aggregation-Induced Emission Luminogens for Enhanced Near-Infrared-II...

Aggregation-induced emission luminogens (AIEgens) used for phototheranostics face an inherent trade-off between radiative decay (fluorescence diagnosis) and nonradiative decay (photothermal therapy, PTT). Herein, we report Staphylococcal protein A (SPA)-imprinted polymer nanoparticles loaded with NIR-II AIEgens (AIE@MIPs) to overcome this limitation. The polymeric network can dynamically expand and contract, stimulated by NIR irradiation, thus subtly releasing or suppressing intramolecular motions of AIEgens in real time to reinforce their intrinsic theranostic natures. At ambient temperature, the rigid imprinted matrix restricts intramolecular rotation to boost NIR-II fluorescence (a 1.5-fold enhancement compared to conventional carriers). Upon 808 nm laser excitation, thermal swelling of the polymer shell releases spatial constraints, facilitating molecular photothermal dissipation (53.3% photothermal conversion efficiency). Moreover, benefiting from Methicillin-resistant Staphylococcus aureus (MRSA) targeting and a positively charged surface, AIE@MIPs achieved enhanced biofilm accumulation and penetration, resulting in superior NIR-II imaging-guided photothermal therapy in mouse models of MRSA biofilm-infected back and joint abscesses. During this process, the NPs caused leakage of intracellular proteins and nucleic acids, impaired bacterial adhesion, and suppressed biofilm metabolic activity. Transcriptome analysis further demonstrated that AIE@MIPs modulated genes involved in inflammatory and immune pathways, showing their great potential in fluorescence-guided precision theranostics for associated clinical diseases. STATEMENT OF SIGNIFICANCE: This study overcomes the intrinsic trade-off between radiative and non-radiative decay pathways in aggregation-induced emission luminogens (AIEgens) for phototheranostic applications. By encapsulating NIR-II AIEgens within a protein-imprinted polymer network, we dynamically modulate spatial confinement to boost both fluorescence brightness and photothermal efficiency even at reduced loading levels. Furthermore, the synthetic antibody-like polymer shell imparts high-affinity targeting and superior biofilm penetration against methicillin-resistant Staphylococcus aureus (MRSA), facilitating precision delivery to deep-seated infections. This bio-nanoplatform enables effective imaging-guided eradication of MRSA in back and joint abscess models, offering a promising non-antibiotic strategy to combat drug-resistant biofilm-associated infections.