DefinePK

Abstract

 
Background: Antibiotic resistance continues to pose a critical global health threat, diminishing the effectiveness of existing therapies and demanding innovative solutions. Traditional antimicrobials face mounting failure rates, particularly against multidrug-resistant organisms. The combined use of nanoparticles (NPs) and CRISPR/Cas9 gene-editing technology has emerged as a promising dual-action strategy, capable of enhancing drug delivery while simultaneously targeting resistance genes for deletion.
Objective: To systematically review the synergistic effects of nanoparticle-based delivery systems and CRISPR/Cas9-mediated gene disruption in combating antibiotic resistance, assessing their efficacy, safety, and translational potential in preclinical models.
Methods: A systematic review was conducted across PubMed and Google Scholar, screening studies published from January 2015 to March 2025. A total of 1,142 records were identified, with 30 studies meeting inclusion criteria after rigorous screening and quality assessment. Eligible studies involved experimental applications of nanoparticle-assisted CRISPR/Cas9 systems targeting resistance genes in bacterial pathogens. Both in vitro and in vivo outcomes were extracted and analyzed for trends in efficacy, delivery efficiency, and toxicity.
Results: Metallic nanoparticles (e.g., Ag, Au, ZnO) showed >90% inhibition of multidrug-resistant strains in vitro. Lipid and polymeric nanoparticles achieved >80% biofilm penetration and improved CRISPR delivery in 76% of studies. CRISPR/Cas9 systems targeting genes like mecA and blaNDM-1 restored antibiotic susceptibility in 78% of edited strains. Delivery efficiency was 30% higher in planktonic cells compared to biofilm-embedded bacteria. However, challenges included off-target effects, immunogenicity, and inconsistent nanoparticle synthesis protocols.
Conclusion: The dual-action approach of nanoparticle-facilitated CRISPR/Cas9 systems demonstrates significant promise in reversing antibiotic resistance. While preclinical data support its efficacy, further research is essential to refine delivery mechanisms, address biosafety concerns, and enable clinical translation.