DUAL ACTION APPROACH OF NANO PARTICLES AND CRISPR/CAS-9 TO OVERCOME ANTIBIOTIC RESISTANCE; A SYSTEMATIC REVIEW
DOI:
https://doi.org/10.71000/915se539Keywords:
Antibiotic resistance, Nanoparticles, , Biofilm penetration, Off-target effects, Immunogenicity, , CRISPR-Cas Systems, Drug Delivery SystemsAbstract
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.
References
Ganipineni, V. D. P., Gutlapalli, S. D., Danda, S., Garlapati, S. K. P., Fabian, D., Okorie, I., & Paramsothy, J. (2023). Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in Cardiovascular Disease: A Comprehensive Clinical Review on Dilated Cardiomyopathy. Cureus, 15(3).
Allemailem, K. S., Alsahli, M. A., Almatroudi, A., Alrumaihi, F., Alkhaleefah, F. K., Rahmani, A. H., & Khan, A. A. (2022). Current updates of CRISPR/Cas9‐mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management. Cancer Communications, 42(12), 1257-1287.
Turner, N. A., Sharma-Kuinkel, B. K., Maskarinec, S. A., Eichenberger, E. M., Shah, P. P., Carugati, M., ... & Fowler Jr, V. G. (2019). Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nature Reviews Microbiology, 17(4), 203-218.
Murhekar, M. V., Bhatnagar, T., Thangaraj, J. W. V., Saravanakumar, V., Kumar, M. S., Selvaraju, S., ... & Vinod, A. (2021). SARS-CoV-2 seroprevalence among the general population and healthcare workers in India, December 2020–January 2021. International Journal of Infectious Diseases, 108, 145-155.
Sachithanandan, J. S., Deepalakshmi, M., Rajamohamed, H., Mary, P., Mohankumar, M., & Vikashini, S. (2024). Revolutionizing Antimicrobial Solutions Nanotechnology, CRISPR-Cas9 and Innovative Approaches to Combat Drug Resistance in ESKAPE Pathogens. Journal of Pure & Applied Microbiology, 18(2).
Vercauteren, S., Fiesack, S., Maroc, L., Verstraeten, N., Dewachter, L., Michiels, J., & Vonesch, S. C. (2024). The rise and future of CRISPR-based approaches for high-throughput genomics. FEMS microbiology reviews, 48(5), fuae020.
Huang, X., Kon, E., Han, X., Zhang, X., Kong, N., Mitchell, M. J., ... & Tao, W. (2022). Nanotechnology-based strategies against SARS-CoV-2 variants. Nature nanotechnology, 17(10), 1027-1037.
Salverda, M. L., Koomen, J., Koopmanschap, B., Zwart, M. P., & de Visser, J. A. G. (2017). Adaptive benefits from small mutation supplies in an antibiotic resistance enzyme. Proceedings of the National Academy of Sciences, 114(48), 12773-12778.
Murhekar, M. V., Bhatnagar, T., Thangaraj, J. W. V., Saravanakumar, V., Kumar, M. S., Selvaraju, S., ... & Vinod, A. (2021). SARS-CoV-2 seroprevalence among the general population and healthcare workers in India, December 2020–January 2021. International Journal of Infectious Diseases, 108, 145-155.
Balasubramanian, A. R. (2024, July). Decidability and complexity of decision problems for affine continuous VASS. In Proceedings of the 39th Annual ACM/IEEE Symposium on Logic in Computer Science (pp. 1-13).
Duan, C., Cao, H., Zhang, L. H., & Xu, Z. (2021). Harnessing the CRISPR-Cas Systems to Combat Antimicrobial Resistance. Frontiers in Microbiology, 12(August).
Citorik, R. J., Mimee, M., & Lu, T. K. (2014). Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nature biotechnology, 32(11), 1141-1145.
Mohammadian Farsani, A., Mokhtari, N., Nooraei, S., Bahrulolum, H., Akbari, A., Farsani, Z. M., Khatami, S., Ebadi, M. sadat, & Ahmadian, G. (2024). Lipid Nanoparticles: The game-changer in CRISPR-Cas9 genome editing. Heliyon, 10(2), e24606.
Gutlapalli, S. D., Ganipineni, V. D. P., Danda, S., Fabian, D., Okorie, I. J., Paramsothy, J., ... & Umyarova, R. A. (2023). Exploring the potential of broadly neutralizing antibodies for treating SARS-CoV-2 variants of global concern in 2023: a comprehensive clinical review. Cureus, 15(3).
Ali, M. A. (2024). Role of CRISPR-Cas Systems in the Pathogenesis of Periodontal Disease and Precision Periodontal Therapy. 2(2), 38–49.
Javaid, N., & Choi, S. (2021). CRISPR/Cas System and Factors Affecting Its Precision and Efficiency. Frontiers in Cell and Developmental Biology, 9(November), 1–25.
Duan, H., et al. (2021). CRISPR/Cas9-loaded polymeric Nanoparticles for tackling bacterial resistance. Advanced Materials, 33(27), 2008763.
Loureiro, D. B., & Da Silva, M. C. (2019). Nanostructured lipid carriers as tools for antibiotic delivery. International Journal of Pharmaceutics, 572, 118778.
Devi, S. N., et al. (2024). Dual-function nanoparticle platforms for gene editing and antimicrobial activity. Small, 20(5), 2306023.
Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018). Delivering crispr: A review of the challenges and approaches. Drug Delivery, 25(1), 1234–1257.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Ahmar Mukarram, Zain-Ul-Abdin, Muskan Muhammad, Muhammad Sulaiman Saeed, Hira Sharafat, Zainab Ali (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
