Bacterial keratitis (BK) is a serious ocular infection and frequently cause irreversible damage to the corneal tissue and even blindness. Current clinical treatments using antibiotics achieve unsatisfactory outcomes due to the lower bioavailability, high risks of drug resistance and limited therapeutic functions. To address these challenges, we proposed a dual-targeted antibacterial and cascaded immunomodulatory therapy strategy, constructing a multifunctional nanoplatform (HPBH@GLA/AMP) using the 3-aminophenylboric acid (NBA) and hyaluronic acid (HA) co-modified hollow polydopamine (HPDA) to serve as a functional nanocarrier (HPBH) for loading antimicrobial peptide (AMP) and glycyrrhizic acid (GLA). The HPBH@GLA/AMP presented excellent targeting and bactericidal performance to Pseudomonas aeruginosa (P. aeruginosa), coupled with its capacity to alleviate the bacteria-triggered excessive immune response via an ingenious cascaded immunoregulatory process. Notably, the study of underlying anti-inflammatory mechanism revealed that the functional nanocarrier of HPDA could effectively scavenge the reactive oxygen species (ROS) for controlling early inflammatory responses, while inhibit the expression of late mediator high mobility group box 1 (HMGB1) chemokine through released GLA.

Specially, the duel-targeted characteristic enabled this nanoplatform to recognize both the bacteria and inflammatory cells precisely and aggregate the location where bacteria and/or inflammatory cells exist persistently, effectively increased the therapeutic concentration of drugs. Featuring the antibacterial synergistic yet

sequential regulation for the inflammatory response, the HPBH@GLA/AMP achieved satisfactory therapeutic

effects in a BK mouse model in vivo. This study provides a bright prospect for clinical treatment of refractory

bacterial keratitis (BK) and even extended to other immunotherapy in infectious disease