Voluntary‐Opsonization‐Enabled Precision Nanomedicines for Inflammation Treatment

Nanomedicines that target specific blood cells represent an emerging strategy to improve drug biodistribution. However, the protein corona usually disrupts nanomedicine targeting to cells and tissues. Herein, instead of exploring synthetic methods to mitigate the impact of the protein corona, its natural interactions with blood cells are leveraged and turn the protein corona into an active ingredient in treating lung inflammation. It is discovered that molecularly engineered liposomes with inverse phosphocholine lipids rapidly enrich complement fragment iC3b by “voluntary opsonization,” which triggers neutrophil hijacking through complement receptor 3 phagocytosis. This neutrophil targeting is cell‐state dependent as only those activated by acute inflammation display efficient neutrophil reconstruction. The liposome‐loaded neutrophils migrate across the alveolar‐capillary barrier, accumulate in the inflamed lung parenchyma within hours, and release their payloads to kill the bacteria. This work shows that, in addition to biological cells, the protein corona can be a new platform for active and precision nanomedicine. Molecularly engineered liposomes are shown to “hitch‐hike” neutrophils through complementary “voluntary opsonization”. The chemotaxis of neutrophils overcomes the physiological barriers and dramatically enhances the accumulation of nanomedicines in the inflamed lungs for effective inflammation treatment. This strategy opens up new paths for neutrophil‐enabled precision nanomedicines for the treatment of inflammatory diseases.