In
the face of the abundant production of various types of carbapenemases,
the antibacterial efficiency of imipenem, seen as “the last
line of defense”, is weakening. Following, the incidence of
carbapenem-resistant Acinetobacter baumannii (CRAB), which can generate antibiotic-resistant biofilms, is increasing.
Based on the superior antimicrobial activity of silver nanoparticles
against multifarious bacterial strains compared with common antibiotics,
we constructed the IPM@AgNPs-PEG-NOTA nanocomposite (silver nanoparticles
were coated with SH-PEG-NOTA as well as loaded by imipenem) whose
core was a silver nanoparticle to address the current challenge, and
IPM@AgNPs-PEG-NOTA was able to function as a novel smart pH-sensitive
nanodrug system. Synergistic bactericidal effects of silver nanoparticles
and imipenem as well as drug-resistance reversal via protection of
the β-ring of carbapenem due to AgNPs-PEG-NOTA were observed;
thus, this nanocomposite confers multiple advantages for efficient
antibacterial activity. Additionally, IPM@AgNPs-PEG-NOTA not only
offers immune regulation and accelerates tissue repair to improve
therapeutic efficacy in vivo but also can prevent the interaction
of pathogens and hosts. Compared with free imipenem or silver nanoparticles,
this platform significantly enhanced antibacterial efficiency while
increasing reactive oxygen species (ROS) production and membrane damage,
as well as affecting cell wall formation and metabolic pathways. According
to the results of crystal violet staining, LIVE/DEAD backlight bacterial
viability staining, and real-time quantitative polymerase chain reaction
(RT-qPCR), this silver nanocomposite downregulated the levels of ompA
expression to prevent formation of biofilms. In summary, this research
demonstrated that the IPM@AgNPs-PEG-NOTA nanocomposite is a promising
antibacterial agent of security, pH sensitivity, and high efficiency
in reversing resistance and synergistically combatting carbapenem-resistant A. baumannii. In the future, various embellishments
and selected loads for silver nanoparticles will be the focus of research
in the domains of medicine and nanotechnology.