Aug 2026· Nanotechnology· Vol 37, pp. 352001· 0 citations· 163 references
Physics
TL;DR
It is concluded that CRISPR-nanoparticle hybrids offer a transformative platform for precision antimicrobial intervention; however, no clinical trials currently exist for this specific application, and coordinated advances in nanoparticle engineering, safety characterization, and regulatory science are essential for clinical deployment against recalcitrant, multidrug-resistant biofilm infections.
Abstract
Antimicrobial resistance represents a critical global health threat that outpaces the development of new antibiotics. Biofilms impose a multifaceted barrier, comprising an extracellular polymeric substance matrix of polysaccharides, proteins, and extracellular DNA, that limits antibiotic penetration and facilitates horizontal gene transfer of resistance determinants. This review adopts a biofilm-centered engineering framework to evaluate clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nanoparticle hybrids as an emerging precision antimicrobial strategy, analyzing the sequential barriers of matrix penetration, bacterial envelope traversal, intracellular cargo release, and resistance-network reprogramming that determine therapeutic success. Lipid-nanoparticle-mediated CRISPR-Cas9 delivery and gold-nanoparticle CRISPR hybrids have been explored for antimicrobial co-delivery applications; precise, matched quantitative comparisons between nanoparticle platforms specific to biofilm CRISPR delivery remain limited in the primary literature. By precisely targeting quorum-sensing regulators (lasR, rhlR, luxS), resistance genes (mcr-1, mecA, blaNDM-1, blaCTX-M-15), and biofilm structural genes (icaA, icaD, bap, csgD), this platform is designed to convert biofilm from an obstacle into a targetable interface. However, clinical translation faces major hurdles, including manufacturing complexity, immunogenicity, off-target risks, regulatory ambiguity between nanomedicine and gene therapy frameworks, and long-term biosafety concerns such as horizontal gene transfer. This review concludes that CRISPR-nanoparticle hybrids offer a transformative platform for precision antimicrobial intervention; however, no clinical trials currently exist for this specific application, and coordinated advances in nanoparticle engineering, safety characterization, and regulatory science are essential for clinical deployment against recalcitrant, multidrug-resistant biofilm infections.
This review critically examines bacteriophage-based antimicrobials, CRISPR-Cas therapeutic systems, and their emerging integration as CRISPR-armed phages, highlighting their comparative advantages, current limitations, and future potential as promising targeted antimicrobial approach platforms requiring further clinical validation.
Anjaneyulu Musini, V. Yata, S. Bukke et al.· Molecular Biology Reports· 0 citations
This review summarises the current strategies of nanoparticle-mediated CRISPR-Cas9 delivery, including lipid, polymeric, hybrid, inorganic, and biomimetic nanoparticles.
Shouvik Mondal, Kriti Kumari· Advanced International Journ...· 0 citations
Antimicrobial resistance (AMR) in respiratory infections represents a major global health challenge, compounded by biological barriers that limit the effectiveness of conventional antibiotics, including mucus hypersecretion, biofilm formation, and intracellular pathogen persistence. Nanotechnology has emerged as a promising platform for addressing these limitations through advanced drug-delivery strategies. This narrative review provides an integrated overview of nanocarrier systems—including lipid-based (e.g., liposomes, solid lipid nanoparticles), polymeric (e.g., PLGA, chitosan), and inorganic nanoparticles (e.g., silver, gold, zinc oxide)—with emphasis on their pharmaceutical design parameters for pulmonary delivery. Key mechanisms by which nanotechnology enhances antimicrobial efficacy include targeted and controlled drug delivery, improved penetration of mucus and biofilms via surface engineering, synergistic combination therapies, and intrinsic antimicrobial activity through mechanisms such as reactive oxygen species generation. Preclinical studies targeting major respiratory pathogens, including Pseudomonas aeruginosa, Mycobacterium tuberculosis, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus, demonstrate enhanced biofilm disruption, intracellular drug delivery, and reductions in bacterial burden. However, important translational challenges remain, including long-term safety, manufacturing scalability, regulatory complexity, and the potential for microbial adaptation. Future directions focus on stimuli-responsive systems, inhalable formulations, and biomimetic platforms to improve targeting and therapeutic precision. Collectively, nanotechnology represents a delivery-oriented strategy with the potential to enhance existing antimicrobial therapies and support the development of more effective interventions against resistant respiratory infections.
Ghazala Muteeb, R. Siraj· Biomedicines· 0 citations
Overall, CRISPR-based antimicrobial therapy represents a transformative approach to precision infectious disease management, with continued technological innovation, interdisciplinary collaboration, and robust clinical validation expected to facilitate its safe, effective, and clinically accessible implementation against multidrug-resistant pathogens.
Dipankar Mukhopadhyay, Dr. Shilanjali Bhalerao, Dr. Vijayendra Gautam et al.· Genetics and Molecular Resea...· 0 citations
Antimicrobial resistance (AMR) has become one of the defining threats to survival in intensive and neonatal intensive care units, where vulnerable hosts, invasive devices, and heavy empirical antibiotic exposure converge to select for multidrug- and extensively drug-resistant ESKAPE and non-aeruginosa Pseudomonas pathogens. We conducted a narrative-scoping synthesis of the peer-reviewed literature identified through targeted searches and, restricted to English-language articles addressing AMR mechanisms and next-generation, non-traditional therapeutics in critical care; reference lists were hand-searched, and findings were organized thematically rather than statistically pooled. Four convergent, non-traditional pillars emerged — programmable CRISPR-Cas and CRISPRi genomic tools, monoclonal antibodies and bioconjugates, antimicrobial and anticancer peptides (notably proline-rich peptides), and stimuli-responsive nanozymes and exosomal carriers — each capable of bypassing classical resistance mechanisms while, at least in preclinical models, sparing commensal microbiota. Persistent translational barriers include bedside diagnostic blindness to biofilm-embedded organisms, an unresolved neonatal and pediatric pharmacokinetic/pharmacodynamic void, and stewardship frameworks that still largely ignore the human resistome. Bridging bench-to-bedside gaps will require standardized biofilm models, dedicated pediatric PK/PD trials, artificial-intelligence-assisted therapeutic design, and microbiome-conscious stewardship, particularly given resource disparities across low- and middle-income settings.
