The overuse of antibiotics exacerbates the development
of antibiotic-resistant
bacteria, threatening global public health, while most traditional
antibiotics act on specific targets and sterilize through chemical
modes. Therefore, it is a desperate need to design novel therapeutics
or extraordinary strategies to overcome resistant bacteria. Herein,
we report a positively charged nanocomposite PNs-Cur with a hydrodynamic
diameter of 289.6 nm, which was fabricated by ring-opening polymerization
of ε-caprolactone and Z-Lys-
N
-carboxyanhydrides
(NCAs), and then natural curcumin was loaded onto the PCL core of
PNs with a nanostructure through self-assembly, identified through
UV–vis, and characterized by scanning electron microscopy (SEM)
and dynamic light scattering (DLS). Especially, the self-assembly
dynamics of PNs was simulated through molecular modeling to confirm
the formation of a core–shell nanostructure. Biological assays
revealed that PNs-Cur possessed broad-spectrum and efficient antibacterial
activities against both Gram-positive and Gram-negative bacteria,
including drug-resistant clinical bacteria and fungus, with MIC values
in the range of 8–32 μg/mL. Also, in vivo evaluation
showed that PNs-Cur exhibited strong antibacterial activities in infected
mice. Importantly, the nanocomposite did not indeed induce the emergence
of drug-resistant bacterial strains even after 21 passages, especially
showing low toxicity regardless of in vivo or in vitro. The study
of the antibacterial mechanism indicated that PNs-Cur could indeed
destruct membrane potential, change the membrane potential, and cause
the leakage of the cytoplasm. Concurrently, the released curcumin
further plays a bactericidal role, eventually leading to bacterial
irreversible apoptosis. This unique bacterial mode that PNs-Cur possesses
may be the reason why it is not easy to make the bacteria susceptible
to easily produce drug resistance. Overall, the constructed PNs-Cur
is a promising antibacterial material, which provides a novel strategy
to develop efficient antibacterial materials and combat increasingly
prevalent bacterial infections.