Engineered cryo-dead macrophages promote healing of MRSA-infected burn wounds via precise, long-acting photodynamic/antibiotic bacterial killing and broad-spectrum anti-inflammation

Methicillin-resistant Staphylococcus aureus (MRSA)-infected burn wounds suffer from severe bacterial infection (resistant to almost all antibiotics) and intense inflammatory responses, leading to difficulty in wound healing. We designed a multifunctional cryogenic dead macrophage system (Van@AIE-CD-M) for precise, long-acting photodynamic/antibiotic MRSA eradication and broad-spectrum anti-inflammation. Cryo-dead macrophage (CD-M) carriers were prepared by freeze-killing live macrophages in liquid nitrogen, which eliminates the inflammatory side effects while preserving cellular structure and receptors. CD-M were then loaded with a high-performance aggregation-induced emission (AIE) photosensitizer TTVP on the membrane and vancomycin in the cytoplasm, yielding Van@AIE-CD-M. Following dripping onto MRSA-infected burn wounds, Van@AIE-CD-M utilized retained pattern-recognition receptors to bind MRSA, enhancing photodynamic antibacterial efficacy by bringing the bacteria close to the membrane-anchored photosensitizer. Meanwhile, pro-inflammatory cytokine receptors expressed on the Van@AIE-CD-M membrane neutralized multiple pro-inflammatory cytokines through specific receptor-ligand binding, achieving broad-spectrum anti-inflammatory effects. Moreover, Van@AIE-CD-M exhibited sustained vancomycin release, ensuring prolonged anti-infective efficacy. After treatment, Van@AIE-CD-M effectively reduced MRSA burden, pro-inflammatory cytokines, and macrophage M1 polarization, while notably increasing anti-inflammatory IL-10, macrophage M2 polarization, and angiogenesis, ultimately accelerating burn wound healing. This engineered CD-M offers a new strategy for treating burns complicated by drug-resistant bacterial infection and could be extended to other infectious diseases.