A dual-targeting lipid nanoparticle delivery system for precision phage therapy against multidrug-resistant Gram-negative bacteria.

A dual-targeting lipid nanoparticle–chimeric phage (AbLCP) against Pseudomonas aeruginosa achieves up to a 10^3-fold bacterial burden reduction at a 10^3-fold lower effective dose than free polymyxin B in murine infection models.

• Why it matters: Antimicrobial resistance in Gram-negative bacteria limits conventional phage therapy by reducing delivery efficiency and intracellular killing, while systemic toxicity and inflammation remain concerns.
• What they did: AbLCP combines an M13 phage displaying anti-LPS antibodies with polymyxin B conjugation, encapsulated in anti-LPS antibody-functionalized lipid nanoparticles, then tests performance in mouse infection models.
• The result: AbLCP shows 67-fold selective accumulation at infection sites, improves bacterial clearance, attenuates systemic inflammation, preserves gut microbiota, and neutralizes LPS to suppress inflammation while inducing a lethal bacterial stress response.

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