Inherited bacterial resistance and biofilm‐induced local immune inactivation are important factors in the failure of antibiotics to fight against bacterial infections. Herein, antibiotic‐loaded mesoporous nanozymes (HA@MRuO2‐Cip/GOx) are fabricated for overcoming bacterial resistance, and activating the local immunosuppression in biofilm microenvironment (BME). HA@MRuO2‐Cip/GOx are prepared by physical adsorption between ciprofloxacin (Cip) or glucose oxidase (GOx) and MRuO2 NPs, and modified with hyaluronic acid (HA). In vitro, HA@MRuO2‐Cip/GOx cleaves extracellular DNA (eDNA) to disrupt biofilm, thereby enhancing Cip kill planktonic bacteria. Furthermore, HA@MRuO2‐Cip/GOx can induce polarization and enhance phagocytosis of a macrophage‐derived cell line. More importantly, in vivo therapeutic performance confirms that HA@MRuO2‐Cip/GOx can trigger macrophage‐related immunity, and effectively alleviate MRSA‐bacterial lung infections. Accordingly, nanocatalytic therapy combined with targeted delivery of antibiotics could enhance the treatment of bacterial infections.
Zn2+‐induced β‐amyloid protein (Aβ) aggregation and microglia activation are the predominant contributors in Alzheimer's disease (AD). Regulating intracephalic excessive Zn2+ is a promising therapeutic strategy for AD treatment. However, only inhibition of Zn2+ is hardly to repair continuous damages caused by activated microglia. Herein, an intelligent resveratrol‐loaded supramolecular vesicles (RES‐loaded vesicles) with zinc ion chelation function and responsive release capability are constructed to alleviate Aβ fibrillation, oxidative stress, and microglial dysfunction. The resveratrol encapsulation efficiency and drug loading efficiency are calculated to be 49.67% and 7.87%, respectively. In vitro studies demonstrate that the RES‐loaded vesicles can modulate Zn2+‐dependent Aβ aggregation. More importantly, the cargoes will be released in zinc environment and further reprograms microglia from proinflammatory M1 phenotype toward anti‐inflammatory M2 phenotype, which prevents spontaneous neuroinflammation and alleviates cytotoxicity of cultured cells from 29% to 12%. With the stereotactic or intranasal administration, RES‐loaded vesicles can overcome the blood brain barrier, alleviate neuronal apoptosis, neuroinflammation, and ultimately ameliorate cognitive impairment in two AD mouse models. This work provides a new sight for taking advantage of Zn2+ to treat CNS disorders.
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