Harnessing nanomaterials to overcome antimicrobial resistance in Gram-positive bacteria: a systematic review

Abstract

Background:Antimicrobial resistance (AMR) among Gram-positive bacteria has emerged as a significant global health threat, with pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) exhibiting increasing resistance to conventional antibiotics. This systematic review evaluates new advances in nanomaterial-based antimicrobial agents as innovative solutions to combat AMR in Gram-positive bacteria.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies published between 2014 and 2024 were systematically screened and analysed from databases including PubMed, Scopus, Google Scholar, and HINARI. From an initial 1,405 articles, 131 experimental studies that met the inclusion criteria were systematically analysed to harness the advances in nanomaterial-based antimicrobial agents in combating AMR in Gram-positive bacteria.

Results: The included studies demonstrated that various nanomaterials, including silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), zinc oxide nanoparticles (ZnO NPs), copper and copper oxide nanoparticles (Cu/CuO NPs), as well as polymeric and hybrid systems, exhibited potent antibacterial and antibiofilm activities. Key mechanisms of action included bacterial membrane disruption, reactive oxygen species (ROS) generation, intracellular interference, and targeted drug delivery. Many nanomaterials showed enhanced efficacy and synergistic effects when combined with conventional antibiotics, effectively reducing bacterial load and inhibiting biofilm formation in resistant strains like MRSA.

Discussion:Nanomaterials offer a multifaceted approach to overcome the evolving resistance mechanisms in Gram-positive pathogens, showing significant preclinical and clinical success. Despite these substantial preclinical results, challenges such as cytotoxicity, environmental impact, scalability, and the potential for resistance adaptation remain unaddressed. Furthermore, important translational barriers persist, most notably insufficient pharmacokinetic data and unclear regulatory pathways. Future efforts must focus on standardized manufacturing, comprehensive toxicity studies, and robust clinical trials to bridge the gap between laboratory innovation and practical therapeutic application.

Keywords

nanotechnology / nanoparticle / antimicrobial resistance / Gram-positive bacteria / drug delivery systems / antimicrobial peptides / multidrug resistance

References

[1] Ahmed SK, Hussein S, Qurbani K, Ibrahim RH, Fareeq A, Mahmood KA, et al. Antimicrobial resistance: Impacts, challenges, and future prospects. J Med, Surg, Public Health. 2024; 2: 100081.

[2] Collaborators AR; Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Aguilar GR, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399: 629-55.

[3] Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015; 109: 309—18.

[4] Cornaglia G. Fighting infections due to multidrug—resistant Gram—positive pathogens. Clin Microbiol Infect. 2009; 15: 209—11.

[5] Karaman R, Jubeh B, Breijyeh Z. Resistance of Gram—Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches. Molecules. 2020; 25: 2888.

[6] Lade H, Kim J. Molecular Determinants of β—Lactam Resistance in Methicillin—Resistant Staphylococcus aureus (MRSA): An Updated Review. Antibiotics (Basel). 2023; 12: 1362.

[7] Mohanta YK, Chakrabartty I, Mishra AK, Chopra H, Mahanta S, Avula SK, et al. Nanotechnology in combating biofilm: A smart and promising therapeutic strategy. Front Microbiol. 2023; 13: 1028086.

[8] Fergestad ME, Stamsås GA, Angeles DM, Salehian Z, Wasteson Y, Kjos M. Penicillin—binding protein PBP2a provides variable levels of protection toward different β—lactams in Staphylococcus aureus RN4220. Microbiologyopen. 2020; 9: e1057.

[9] Uruén C, Chopo—Escuin G, Tommassen J, Mainar—Jaime RC, Arenas J. Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance. Antibiotics (Basel). 2020; 10: 3.

[10] Muteeb G, Rehman MT, Shahwan M, Aatif M. Origin of Antibiotics and Antibiotic Resistance, and Their Impacts on Drug Development: A Narrative Review. Pharmaceuticals (Basel). 2023; 16: 1615.

[11] Parvin N, Joo SW, Mandal TK. Nanomaterial—Based Strategies to Combat Antibiotic Resistance: Mechanisms and Applications. Antibiotics (Basel). 2025; 14: 207.

[12] Rajchakit U, Sarojini V. Recent Developments in Antimicrobial—Peptide—Conjugated Gold Nanoparticles. Bioconjug Chem. 2017; 28: 2673-86.

[13] Chen N, Liao Y, Lin P, Chen W, Wen Z, Hsieh S. Investigation of the Characteristics and Antibacterial Activity of Polymer—Modified Copper Oxide Nanoparticles. Int J Mol Sci. 2021; 22: 12913.

[14] Chandrasekaran M, Kim K, Chun S. Antibacterial Activity of Chitosan Nanoparticles: A Review. Processes. 2020; 8: 1173.

[15] Hameed S, Sharif S, Ovais M, Xiong H. Emerging trends and future challenges of advanced 2D nanomaterials for combating bacterial resistance. Bioact Mater. 2024; 38: 225-57.

[16] Srivastava P, Kim Y, Cho H, Kim K. Synergistic Action between Copper Oxide (CuO) Nanoparticles and Anthraquinone—2—Carboxylic Acid (AQ) against Staphylococcus aureus. J Compos Sci. 2023; 7: 135.

[17] Jacobowski AC, Boleti APA, Cruz MV, Santos KFDP, Andrade LRMd, Frihling BEF, et al. Combating Antimicrobial Resistance: Innovative Strategies Using Peptides, Nanotechnology, Phages, Quorum Sensing Interference, and CRISPR—Cas Systems. Pharmaceuticals (Basel). 2025; 18: 1119.

[18] Rawson TM, Wilson RC, OʼHare D, Herrero P, Kambugu A, Lamorde M, et al. Optimizing antimicrobial use: challenges, advances and opportunities. Nat Rev Microbiol. 2021; 19: 747-58.

[19] Yasmin N, Hameed S, Javed R, Ahmed S, Imran M. Inactivation of foodborne pathogens on food packaging and in cow milk by exposure to a Nd:YAG laser. Can J Phys. 2017; 95: 662—9.

[20] Huang X, Chen X, Chen Q, Yu Q, Sun D, Liu J. Investigation of functional selenium nanoparticles as potent antimicrobial agents against superbugs. Acta Biomater. 2016; 30: 397-407.

[21] Nawaz A, Ali SM, Rana NF, Tanweer T, Batool A, Webster TJ, et al. Ciprofloxacin—Loaded Gold Nanoparticles against Antimicrobial Resistance: An In Vivo Assessment. Nanomaterials (Basel). 2021; 11: 3152.

[22] Nithiyavathi R, Sundaram SJ, Anand GT, Kumar DR, Raj AD, Farraj DAA, et al. Gum mediated synthesis and characterization of CuO nanoparticles towards infectious disease—causing antimicrobial resistance microbial pathogens. J Infect Public Health. 2021; 14: 1893-902.

[23] Manzoor S, Bashir DJ, Imtiyaz K, Rizvi MMA, Ahamad I, Fatma T, et al. Biofabricated platinum nanoparticles: therapeutic evaluation as a potential nanodrug against breast cancer cells and drug—resistant bacteria. RSC Adv. 2021; 11: 24900—16.

[24] Huang T, Holden JA, Reynolds EC, Heath DE, OʼBrien—Simpson NM, OʼConnor AJ. Multifunctional Antimicrobial Polypeptide—Selenium Nanoparticles Combat Drug—Resistant Bacteria. ACS Appl Mater Interfaces. 2020; 12: 55696-709.

[25] Chaurasia AK, Thorat ND, Tandon A, Kim J, Park SH, Kim KK. Coupling of radiofrequency with magnetic nanoparticles treatment as an alternative physical antibacterial strategy against multiple drug resistant bacteria. Sci Rep. 2016; 6: 33662.

[26] Goel N, Ahmad R, Singh R, Sood S, Khare SK. Biologically synthesized silver nanoparticles by Streptomyces sp. EMB24 extracts used against the drug—resistant bacteria. Bioresour Technol Rep. 2021; 15: 100753.

[27] Yuan Q, Zhao Y, Zhang Z, Tang Y. On—Demand Antimicrobial Agent Release from Functionalized Conjugated Oligomer—Hyaluronic Acid Nanoparticles for Tackling Antimicrobial Resistance. ACS Appl Mater Interfaces. 2021; 13: 257-65.

[28] Ashajyothi C, Harish KH, Dubey N, Chandrakanth RK. Antibiofilm activity of biogenic copper and zinc oxide nanoparticles—antimicrobials collegiate against multiple drug resistant bacteria: a nanoscale approach. J Nanostruct Chem. 2016; 6: 329-41.

[29] Sanyasi S, Majhi RK, Kumar S, Mishra M, Ghosh A, Suar M, et al. Polysaccharide—capped silver Nanoparticles inhibit biofilm formation and eliminate multi—drug—resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells. Sci Rep. 2016; 6: 24929.

[30] Morellá—Aucejo Á, Medaglia S, Ruiz—Rico M, Martínez—Máñez R, Marcos MD, Bernardos A. Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new “nanokiller” approach in the era of antimicrobial resistance. Biomater Adv. 2024; 160: 213840.

[31] Cai L, Zhu X, Ruan H, Yang J, Wei W, Wu Y, et al. Curcumin—stabilized silver nanoparticles encapsulated in biocompatible electrospun nanofibrous scaffold for sustained eradication of drug—resistant bacteria. J Hazard Mater. 2023; 452: 131290.

[32] Sathishkumar RS, Sundaramanickam A, Srinath R, Ramesh T, Saranya K, Meena M, et al. Green synthesis of silver nanoparticles by bloom forming marine microalgae Trichodesmium erythraeum and its applications in antioxidant, drug—resistant bacteria, and cytotoxicity activity. J Saudi Chem Soc. 2019; 23: 1180-91.

[33] Zhu Y, Xu J, Wang Y, Chen C, Gu H, Chai Y, et al. Silver nanoparticles—decorated and mesoporous silica coated single—walled carbon nanotubes with an enhanced antibacterial activity for killing drug—resistant bacteria. Nano Res. 2020; 13: 389-400.

[34] Yao Z, Zhang Z, Zhang J, Li J, Gao G, Sun T. Charge Effect of Mercaptobenzimidazole—Modified Ultrasmall Gold—Nanoparticles against Drug—Resistant Bacteria. ACS Appl Bio Mater. 2024; 7: 3330—6.

[35] Alzoubi F, BaniHani W, BaniHani R, Al—Khateeb H, Al—Qadi M, Bataineh QA. Synthesis and Characterization of Silver Nanoparticles (Ag), Magnetite Nanoparticles (Fe₃O₄), and Magnetite/Silver Core—Shell (Fe₃O₄/Ag) Nanoparticles, and Their Application against Drug—Resistant Bacteria. J Clust Sci. 2024; 35: 2979-89.

[36] Pramanik A, Gates K, Gao Y, Zhang Q, Han FX, Begum S, et al. Composites Composed of Polydopamine Nanoparticles, Graphene Oxide, and ε—Poly—L—lysine for Removal of Waterborne Contaminants and Eradication of Superbugs. ACS Appl Nano Mater. 2019; 2: 3339-47.

[37] Xue Y, Wang C, Zhao Y, Zhao Z, Cui R, Du B, et al. Mixed—charge hyperbranched polymer nanoparticles with selective antibacterial action for fighting antimicrobial resistance. Acta Biomater. 2024; 189: 545-58.

[38] Olatunji AO, Varghese N, Lakkimsetti M, Rahman MM, Abosaoda MK, Ahmad W, et al. Combating Antimicrobial Resistance With Nanotechnology Developing New Antimicrobial Agents And Coatings. Nanotechnol Perceptions. 2024; 20: 734-61.

[39] Jain A, Kongkham B, Puttaswamy H, Butola BS, Malik HK, Malik A. Development of Wash—Durable Antimicrobial Cotton Fabrics by In Situ Green Synthesis of Silver Nanoparticles and Investigation of Their Antimicrobial Efficacy against Drug—Resistant Bacteria. Antibiotics (Basel). 2022; 11: 864.

[40] Lu B, Lu F, Ran L, Yu K, Xiao Y, Li Z, et al. Self—assembly of natural protein and imidazole molecules on gold nanoparticles: Applications in wound healing against multi—drug resistant bacteria. Int J Biol Macromol. 2018; 119: 505—16.

[41] Xie N. Synthesis and antibacterial effects of silver nanoparticles (AgNPs) against multi—drug resistant bacteria. Biomed Mater Eng. 2024; 35: 451-63.

[42] Nijil S, Bhat SG, Kedla A, Thomas MR, Kini S. A silver lining in MRSA treatment: The synergistic action of poloxamer—stabilized silver nanoparticles and methicillin against antimicrobial resistance. Microb Pathog. 2024; 197: 107087.

[43] Yaseen B, Gangwar C, Nayak R, Kumar I, Sarkar J, Baker A, et al. Cannabis sativa mediated palladium nanoparticles as an effective nanodrug against multi—drug resistant bacteria and A549 lung cancer cells. Inorg Chem Commun. 2023; 157: 111254.

[44] Akbar N, Kawish M, Jabri T, Khan NA, Shah MR, Siddiqui R. Enhancing efficacy of existing antibacterials against selected multiple drug resistant bacteria using cinnamic acid—coated magnetic iron oxide and mesoporous silica nanoparticles. Pathog Glob Health. 2022; 116: 438-54.

[45] Hodhod MS, Gaafar ARZ, AlMunqedhi BM, Elzein A, Abdelmalik AM. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug—resistant bacteria. Open Chem. 2024; 22: 20230184.

[46] Afolayan EM, Afegbua SL, Ado SA. Characterization and antibacterial activity of silver nanoparticles synthesized by soil—dwelling Bacillus thuringiensis against drug—resistant bacteria. Biologia. 2023; 78: 2283-92.

[47] Mendez—Pfeiffer P, Ballesteros—Monrreal MG, Gaona—Ochoa J, Juarez J, Gastelum—Cabrera M, Montaño—Leyva B, et al. Biosynthesis of Silver Nanoparticles Using Seasonal Samples of Sonoran Desert Propolis: Evaluation of Its Antibacterial Activity against Clinical Isolates of Multi—Drug Resistant Bacteria. Pharmaceutics. 2022; 14: 1853.

[48] Lai L, Zou W, Zhang Y, Tu Y, Li S, Xin T, et al. Multifunctional MIL—101 nanoparticles with Fenton—like reactions to Co—deliver LL—37 peptide and Vancomycin for targeted NIR imaging and Drug—resistant bacteria treatment. Chem Eng J. 2022; 435: 135084.

[49] Jayalakshmi S, Singaravelu DK, Mariappan M, Ameen F, Veerappan A. Sunlight—assisted synthesis of bimetallic silver—copper nanoparticles using peanut shell extract and its reusable activity against drug—resistant bacteria. New J Chem. 2024; 48: 17310-20.

[50] Sabzevar AH, Hashemitabar GR, Rad M, Vatandoost J. Synthesis and Biological Properties of Silver Chloride Nanoparticles Using Cell—free Extracts of Aeromonas hydrophila and Antibacterial Activity against Drug—Resistant Bacteria. Braz arch biol technol. 2021; 64: e21210010.

[51] Atanda SA, Shaibu OR, Agunbiade FO, Arotiba O. Facile Synthesis and Characterization of Chitosan Nanoparticles from Archachatina marginata Shell as Potential Solution to Antimicrobial Resistance. BioNanoSci. 2024; 14: 3188-203.

[52] Yu J, Xu H, Wei J, Niu L, Zhu H, Jiang C. Bacteria—Targeting Nanoparticles with ROS—Responsive Antibiotic Release to Eradicate Biofilms and Drug—Resistant Bacteria in Endophthalmitis. Int J Nanomedicine. 2024; 19: 2939—56.

[53] Sangappa M, Thiagarajan P. Combating drug resistant pathogenic bacteria isolated from clinical infections, with silver oxide nanoparticles. Indian J Pharm Sci. 2015; 77: 151—5.

[54] Gharieb MM, Elkemary MA, Hassan AM, Gomaa SM. Antibacterial activity of Silver Nanoparticles Biosynthesized by Zingiber officinale on Multi—Drug Resistant Bacteria. DJS. 2024; 48: 94-119.

[55] Sharma G, Sharma R, Mishra V, Rajni E, Mamoria VP. Green Synthesis of Iron Oxide Nanoparticles and Their Efficacy against Multi Drug Resistant Bacteria and Fungi. Russ J Appl Chem. 2022; 95: 1187—98.

[56] Mala R, Ruby Celsia AS. Isolation and identification of burn wound superbugs by molecular technique and their susceptibility to silver nanoparticles. IOP Conf Ser: Mater Sci Eng. 2018; 310: 012146.

[57] Abdul Hadi A, Malek NANN, Matmin J, Asraf MH, Susanto H, Mohammad Din S, et al. Synergistic antibacterial effect of Persicaria odorata synthesised silver nanoparticles with antibiotics on drug—resistant bacteria. Inorg Chem Commun. 2024; 159: 111725.

[58] Novickij V, Stanevičienė R, Vepštaitė—Monstavičė I, Gruškienė R, Krivorotova T, Sereikaitė J, et al. Overcoming Antimicrobial Resistance in Bacteria Using Bioactive Magnetic Nanoparticles and Pulsed Electromagnetic Fields. Front Microbiol. 2018; 8: 2678.

[59] Achamo T, Zereffa EA, Murthy HCA, Venkatesha Perumal R, Balachandran R. Phyto—mediated synthesis of copper oxide nanoparticles using Artemisia abyssinica leaf extract and its antioxidant, antimicrobial and DNA binding activities. Green Chem Lett Rev. 2022; 15: 598-614.

[60] Shirzadi—Ahodashti M, Hashemi Z, Mortazavi Y, Khormali K, Mortazavi—Derazkola S, Ebrahimzadeh MA. Discovery of high antibacterial and catalytic activities against multi—drug resistant clinical bacteria and hazardous pollutants by biosynthesized of silver nanoparticles usingStachys inflata extract (AgNPs@SI). Colloids Surf A Physicochem Eng Asp. 2021; 617: 126383.

[61] El—Aziz NKA, Ammar AM, El—Naenaeey EYM, Damaty HME, Elazazy AA, Hefny AA, et al. Antimicrobial and antibiofilm potentials of cinnamon oil and silver nanoparticles against Streptococcus agalactiae isolated from bovine mastitis: new avenues for countering resistance. BMC Vet Res. 2021; 17: 136.

[62] Asvar Z, Pirbonyeh N, Emami A, Hashemi S, Fadaie M, Ebrahiminezhad A, et al. Enhancing antibacterial activity against multi—drug resistant wound bacteria: Incorporating multiple nanoparticles into chitosan—based nanofibrous dressings for effective wound regeneration. J Drug Deliv Sci Technol. 2024; 95: 105542.

[63] Žalnėravičius R, Mikalauskaitė A, Niaura G, Paškevičius A, Jagminas A. Ultra—small methionine—capped Au⁰/Au⁺ nanoparticles as efficient drug against the antibiotic—resistant bacteria. Mater Sci Eng C Mater Biol Appl. 2019; 102: 646—52.

[64] Farzanegan F, Shahabi M, Niazi AE, Soleimanpour S, Shafaee H, Rangrazi A. Effect of the addition of Chitosan and TiO₂ nanoparticles on antibacterial properties of an orthodontic composite in fixed orthodontic treatment: a randomized clinical trial study. Biomed Phys Eng Express. 2021; 7: 045017.

[65] Oliveira MS, Paula MSA, Cardoso MM, Silva NP, Tavares LCD, Gomes TV, et al. Exploring the antimicrobial efficacy of tea tree essential oil and chitosan against oral pathogens to overcome antimicrobial resistance. Microb Pathog. 2024; 196: 107006.

[66] Vadakkan K, Hemapriya J, Ngangbam AK, Sathishkumar K, Mapranathukaran VO. Biofilm inhibition of Staphylococcus aureus by silver nanoparticles derived from Hellenia speciosa rhizome extract. Microb Pathog. 2024; 196: 106933.

[67] Ye Y, Zheng Q, Wang Z, Wang S, Lu Z, Chu Q, et al. Metal—phenolic nanoparticles enhance low temperature photothermal therapy for bacterial biofilm in superficial infections. J Nanobiotechnology. 2024; 22: 713.

[68] Geng X, Wei Y, Li Y, Zhao S, Li Z, Li H, et al. Antimicrobial Activity of Nano—GeO₂/CTAB Complex Against Fungi and Bacteria Isolated from Paper. Int J Mol Sci. 2024; 25: 13541.

[69] Fatih HJ, Ashengroph M, Sharifi A, Zorab MM. Green—synthesized α—Fe₂O₃—nanoparticles as potent antibacterial, anti—biofilm and anti—virulence agent against pathogenic bacteria. BMC Microbiol. 2024; 24: 535.

[70] Mayattu K, Rajwade J, Ghormade V. Development of erythromycin loaded PLGA nanoparticles for improved drug efficacy and sustained release against bacterial infections and biofilm formation. Microb Pathog. 2024; 197: 107083.

[71] Rahmanian N, Moulavi P, Ashrafi F, Sharifi A, Asadi S. Surface—functionalized UIO—66—NH₂ for dual—drug delivery of vancomycin and amikacin against vancomycin—resistantStaphylococcus aureus. BMC Microbiol. 2024; 24: 462.

[72] Jibrin F, Fanoro OT, Maluleke R, Lebepe TC, Mgedle N, Mbaz GIM, et al. Biosynthesis, Characterization, and Antibacterial Activity of Gold, Silver, and Bimetallic Nanoparticles Using Annona squamosa L. Leaves. Antibiotics (Basel). 2024; 13: 1199.

[73] Jiang T, Chen W, Lu C, Yang J, Zeng Z, Li W, et al. A Multifunctional Nanozyme Integrating Antioxidant, Antimicrobial and Pro—Vascularity for Skin Wound Management. Int J Nanomedicine. 2024; 19: 3217-32.

[74] Luo Y, Jia X, Wu X, Diao L, Zhao Y, Liu X, et al. Bacteria—activated macrophage membrane coated ROS—responsive nanoparticle for targeted delivery of antibiotics to infected wounds. J Nanobiotechnology. 2024; 22: 781.

[75] Ali AY, Alani AK, Ahmed BO, Hamid LL. Effect of biosynthesized silver nanoparticle size on antibacterial and anti—biofilm activity against pathogenic multi—drug resistant bacteria. OpenNano. 2024; 20: 100213.

[76] Xiang Y, Yan L, Deng L, Tang D, Liu X, Lin J, et al. Multiple enzyme—mimic polypeptide based carbon nanoparticles by ROP and Fe coordination for ROS regulation and photo—thermal therapy against bacterial infection. Int J Biol Macromol. 2024; 281: 136461.

[77] Abouhashim MM, Swidan MM, Ibrahim AB, Gharieb MM, Sakr TM. Appraising the antibacterial/antioxidant activities of vancomycin as a novel nano—platfom: Characterization, in—vitro assessment and in—vivo radio—tracking in animal models. J Drug Deliv Sci Technol. 2024; 96: 105732.

[78] Karthikeyan A, Gopinath N, Nair BG. Ecofriendly biosynthesis of copper nanoparticles from novel marine S. rhizophila species for enhanced antibiofilm, antimicrobial and antioxidant potential. Microb Pathog. 2024; 194: 106836.

[79] Dharshini KS, Ameen F, Anbazhagan V. Mechanistic Investigation on the Antibacterial Activity of Biogenic Silver Nanoparticles Prepared Using Root Extract of Sarsaparilla and Demonstrated their In Vivo Efficacy in Zebrafish Model. Curr Microbiol. 2024; 81: 268.

[80] Asif M, Fakhar—E—Alam M, Tahir M, Jamil F, Sardar H, Rehman J, et al. Synthesis, Characterization, and Evaluation of the Antimicrobial and Anticancer Activities of Zinc Oxide and Aluminum—Doped Zinc Oxide Nanocomposites. Pharmaceuticals (Basel). 2024; 17: 1216.

[81] Najafabadi SS, Doudi M, Tahmourespour A, Amiri G, Rezayatmand Z. Assessment of Antimicrobial Activity of Chitosan, ZnO, and Urtica dioica—ZnO NPs Against Staphylococcus aureus Isolated from Diabetic Ulcers. Curr Microbiol. 2024; 81: 295.

[82] Rilievo G, Cencini A, Cecconello A, Currò S, Bortoletti M, Leszczyńska K, et al. Interactions between prokaryotic polysaccharides and colloidal magnetic nanoparticles for bacteria removal: A strategy for circumventing antibiotic resistance. Int J Biol Macromol. 2024; 274: 133415.

[83] Wang Q, Zhao J, Huang T, Sun C, Chen W, Zou H, et al. Oxygen vacancy—rich nickel oxide nanoplatforms for enhanced photothermal and chemodynamic therapy combat methicillin—resistant Staphylococcus aureus. Acta Biomater. 2024; 182: 275-87.

[84] Fagbemi KO, Thonda OA, Daramola OO, Oyewole T, Adeduro OO, Samuel A, et al. Antibacterial Activity of Silver Nanoparticles Synthesized Using Vitex grandifolia Against Multidrug—Resistant (MDR) Pathogens. Trop J Nat Prod Res. 2024; 8: 8068-74.

[85] Wintachai P, Jaroensawat N, Harding P, Wiwasuku T, Mitsuwan W, Septama AW. Antibacterial and antibiofilm efficacy of Solanum lasiocarpum root extract synthesized silver/silver chloride nanoparticles against Staphylococcus haemolyticus associated with bovine mastitis. Microb Pathog. 2024; 192: 106724.

[86] Malaikozhundan B, Mohandoss S, Krishnamoorthi R, Bharathi PV, Palanisamy S, Vinodhini J. Enhanced bactericidal, antibiofilm and antioxidative response of Lawsonia inermis leaf extract synthesized ZnO NPs loaded with commercial antibiotic. Bioprocess Biosyst Eng. 2024; 47: 1241—57.

[87] Hussein S, Sulaiman S, Ali S, Pirot R, Qurbani K, Hamzah H, et al. Synthesis of Silver Nanoparticles from Aeromonas caviae for Antibacterial Activity and In Vivo Effects in Rats. Biol Trace Elem Res. 2024; 202: 2764—75.

[88] Ansari MA, Alomary MN. Bioinspired ferromagnetic NiFe₂O₄ nanoparticles: Eradication of fungal and drug—resistant bacterial pathogens and their established biofilm. Microb Pathog. 2024; 193: 106729.

[89] Gonçalves RR, Peixoto D, Costa RR, Franco AR, Castro VIB, Pires RA, et al. Antibacterial properties of photo—crosslinked chitosan/methacrylated hyaluronic acid nanoparticles loaded with bacitracin. Int J Biol Macromol. 2024; 277: 134250.

[90] Costabile G, Baldassi D, Müller C, Groß B, Ungaro F, Schubert S, et al. Antibiotic—loaded nanoparticles for the treatment of intracellular methicillin—resistant Staphylococcus Aureus infections: In vitro and in vivo efficacy of a novel antibiotic. J Control Release. 2024; 374: 454-65.

[91] Abdelrahman SESAH, Hawary SE, Mohsen E, Raey MAE, Selim HMRM, Hamdan AME, et al. Bio—fabricated zinc oxide nanoparticles mediated by endophytic fungus Aspergillus sp. SA17 with antimicrobial and anticancer activities: in vitro supported by in silico studies. Front Microbiol. 2024; 15: 1366614.

[92] Lokhande AS, Maurya V, Rani K, Parashar P, Gaind R, Tandon V, et al. Polydispersity—mediated high efficacy of an in—situ aqueous nanosuspension of PPEF.3HCl in methicillin resistantStaphylococcus aureus sepsis model. Int J Pharm. 2024; 655: 123982.

[93] Crisan MC, Pandrea SL, Matros L, Mocan T, Mocan L. In vitro antimicrobial activity of silver nanoparticles against selected Gram—negative and Gram—positive pathogens. Med Pharm Rep. 2024; 97: 280-97.

[94] Nawaz MZ, Alghamdi HA, Zahoor M, Rashid F, Alshahrani AA, Alghamdi NS, et al. Synthesis of novel metal silica nanoparticles exhibiting antimicrobial potential and applications to combat periodontitis. Environ Res. 2024; 241: 117415.

[95] Qi L, Wang X, Huang J, Yue T, Lu Y, San D, et al. Silver Nanoparticles Encapped by Dihydromyricetin: Optimization of Green Synthesis, Characterization, Toxicity, and Anti—MRSA Infection Activities for Zebrafish (Danio rerio). Int J Mol Sci. 2024; 25: 5255.

[96] Hayee R, Iqtedar M, Albekairi NA, Alshammari A, Makhdoom MA, Islam M, et al. Levofloxacin loaded chitosan and poly—lactic—co—glycolic acid nano—particles against resistant bacteria: Synthesis, characterization and antibacterial activity. J Infect Public Health. 2024; 17: 906— 17.

[97] Rabbi F, Nisar A, Saeed A. Biosynthesis, Characterization and Antimicrobial Response of Silver Nanoparticles Using an Aqueous Extract of Taraxacum officinale. Pharm Chem J. 2024; 58: 275-81.

[98] Mishra M, Ballal A, Rath D, Rath A. Novel silver nanoparticle—antibiotic combinations as promising antibacterial and anti—biofilm candidates against multiple—antibiotic resistant ESKAPE microorganisms. Colloids Surf B Biointerfaces. 2024; 236: 113826.

[99] Wang C, Xiao R, Yang Q, Pan J, Cui P, Zhou S, et al. Green synthesis of epigallocatechin gallate—ferric complex nanoparticles for photothermal enhanced antibacterial and wound healing. Biomed Pharmacother. 2024; 171: 116175.

[100] Ferreyra Maillard APV, Bordón A, Cutro AC, Dalmasso PR, Hollmann A. Green One—Step Synthesis of Silver Nanoparticles Obtained from Schinus areira Leaf Extract: Characterization and Antibacterial Mechanism Analysis. Appl Biochem Biotechnol. 2024; 196: 1104-21.

[101] Almutleb ES, Ramachandran S, Khan AA, El—Hiti GA, Alanazi SA. Synergistic Effect of Nilavembu Choornam—Gold Nanoparticles on Antibiotic—Resistant Bacterial Susceptibility and Contact Lens Contamination—Associated Infectious Pathogenicity. Int J Mol Sci. 2024; 25: 2115.

[102] Hutagalung RA, Giovani, Simanjuntak K, Fauziah C, Yusmaini H, Bahar M, et al. Green Synthesis of Gold Nanoparticles with Manilkara zapota Leaf Extract and Its Application as Antibacterial Agent. RJPT. 2024; 17: 5509—14.

[103] Rahman A, Kafi MA, Beak G, Saha SK, Roy KJ, Habib A, et al. Green Synthesized Chitosan Nanoparticles for Controlling Multidrug—Resistant mecA— and blaZ—Positive Staphylococcus aureus and aadA1—Positive Escherichia coli. Int J Mol Sci. 2024; 25: 4746.

[104] Rajchakit U, Lamba S, Wang K, Lyons N, Lu J, Swift S, et al. Size—Controlled Synthesis of Gold Nanoparticles Tethering Antimicrobial Peptides with Potent Broad—Spectrum Antimicrobial and Antibiofilm Activities. Mol Pharm. 2024; 21: 596-608.

[105] Abd Ali MA, Shareef AA. Antibacterial Activity of Silver Nanoparticles Derived from Extracellular Extract of Enterococcus aerogenes Against Dental Disease Bacteria Isolated. Regen Eng Transl Med. 2024; 10: 68-77.

[106] Sewid AH, Sharaf M, El—Demerdash AS, Ragab SM, Al—Otibi FO, Yassin MT, et al. Hexagonal zinc oxide nanoparticles: a novel approach to combat multidrug—resistant Enterococcus faecalis biofilms in feline urinary tract infections. Front Cell Infect Microbiol. 2025; 14: 1505469.

[107] Liu Y, Lan Q, Liu J, Shi Y, Wu Q, Wang Q, et al. Phenylboronic acid—functionalized BSA@CuS@PpIX nanoparticles for enhanced antibacterial photodynamic/photothermal therapy. J Drug Delivery Sci Technol. 2023; 88: 104965.

[108] El Fadl FIA, Hegazy DE, Maziad NA, Ghobashy MM. Effect of nano—metal oxides (TiO₂, MgO, CaO, and ZnO) on antibacterial property of (PEO/PEC—co—AAm) hydrogel synthesized by gamma irradiation. Int J Biol Macromol. 2023; 250: 126248.

[109] Gomaa NH, El—Aziz NKA, El—Naenaeey EY, Abdelaziz WS, Sewid AH. Antimicrobial potential of myricetin—coated zinc oxide nanocomposite against drug—resistant Clostridium perfringens. BMC Microbiol. 2023; 23: 79.

[110] Arafa MG, Mousa HA, Kataia MM, M S, Afifi NN. Functionalized surface of PLGA nanoparticles in thermosensitive gel to enhance the efficacy of antibiotics against antibiotic resistant infections in endodontics: A randomized clinical trial. Int J Pharm X. 2023; 6: 100219.

[111] Karimitabar Z, Farmani A, Azimzadeh M, Alikhani MS, Moghadam Shakib M, Alikhani MY. The Antimicrobial Activity of Propolis Ethanolic Extract and Silver Nanoparticles Synthesized by Green Method on Gram—Positive and Negative Bacteria. Avicenna J Clin Microbiol Infect. 2023; 10: 131-6.

[112] Younis AB, Milosavljevic V, Fialova T, Smerkova K, Michalkova H, Svec P, et al. Synthesis and characterization of TiO₂ nanoparticles combined with geraniol and their synergistic antibacterial activity. BMC Microbiol. 2023; 23: 207.

[113] Messaoudi O, Benamar I, Azizi A, Albukhaty S, Khane Y, Sulaiman GM, et al. Characterization of Silver Carbonate Nanoparticles Biosynthesized Using Marine Actinobacteria and Exploring of Their Antimicrobial and Antibiofilm Activity. Mar Drugs. 2023; 21: 536.

[114] Sarıipek FB. Biopolymeric nanofibrous scaffolds of poly(3—hydroxybuthyrate)/chitosan loaded with biogenic silver nanoparticle synthesized using curcumin and their antibacterial activities. Int J Biol Macromol. 2024; 256: 128330.

[115] Alamri H, Chen G, Huang SD. Development of Biocompatible Ga₂(HPO₄)₃ Nanoparticles as an Antimicrobial Agent with Improved Ga Resistance Development Profile against Pseudomonas aeruginosa. Antibiotics (Basel). 2023; 12: 1578.

[116] Alemu FW, Zeleke TD. Green synthesis of silver and cobalt oxide nanoparticles using Croton macrostaychus plant extract and evaluation of their antibacterial activity. Nanomed J. 2024; 11: 80-92.

[117] Adnan M, Siddiqui AJ, Ashraf SA, Ashraf MS, Alomrani SO, Alreshidi M, et al. Saponin—Derived Silver Nanoparticles from Phoenix dactylifera (Ajwa Dates) Exhibit Broad—Spectrum Bioactivities Combating Bacterial Infections. Antibiotics (Basel). 2023; 12: 1415.

[118] Mandal S, Hwang S, Marpu SB, Omary MA, Prybutok V, Shi SQ. Bioinspired Synthesis of Silver Nanoparticles for the Remediation of Toxic Pollutants and Enhanced Antibacterial Activity. Biomolecules. 2023; 13: 1054.

[119] Francis DV, Jayakumar MN, Ahmad H, Gokhale T. Antimicrobial Activity of Biogenic Metal Oxide Nanoparticles and Their Synergistic Effect on Clinical Pathogens. Int J Mol Sci. 2023; 24: 9998.

[120] Giráldez—Pérez RM, Grueso EM, Carbonero A, Álvarez Márquez J, Gordillo M, Kuliszewska E, et al. Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance. Antibiotics (Basel). 2023; 12: 1275.

[121] Gómez NC, Manetsberger J, Benomar N, Abriouel H. Novel combination of nanoparticles and metallo—β—lactamase inhibitor/antimicrobial—based formulation to combat antibiotic resistant Enterococcus sp. and Pseudomonas sp. strains. Int J Biol Macromol. 2023; 248: 125982.

[122] Elhabak M, Shebl RI, Omar S. Modulating liposomal nanoparticles to enhance uptake and targeting of methicillin—resistant Staphylococcus aureus. Future Microbiol. 2023; 18: 343-55.

[123] AbdElrahman TKAA, Gebreel HMA, Youssef HIA. Assessing the effectiveness of green synthesized zinc oxide nanoparticles in controlling multidrug—resistant clinical bacteria. Indian J Microbiol. 2023; 63: 65-72.

[124] Jambhrunkar M, Maghrebi S, Doddakyathanahalli D, Wignall A, Prestidge CA, Bremmell KE. Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages. Pharmaceutics. 2023; 15: 1037.

[125] Ugalde—Arbizu M, Aguilera—Correa JJ, Sebastian ES, Páez PL, Nogales E, Esteban J, et al. Antibacterial Properties of Mesoporous Silica Nanoparticles Modified with Fluoroquinolones and Copper or Silver Species. Pharmaceuticals (Basel). 2023; 16: 961.

[126] Rata DM, Cadinoiu AN, Daraba OM, Gradinaru LM, Atanase LI, Ichim DL. Influence of ZnO Nanoparticles on the Properties of Ibuprofen—Loaded Alginate—Based Biocomposite Hydrogels with Potential Antimicrobial and Anti—Inflammatory Effects. Pharmaceutics. 2023; 15: 2240.

[127] Dove AS, Dzurny DI, Dees WR, Qin N, Rodriguez CCN, Alt LA, et al. Silver nanoparticles enhance the efficacy of aminoglycosides against antibiotic—resistant bacteria. Front Microbiol. 2023; 13: 1064095.

[128] Asif N, Fatima S, Siddiqui T, Fatma T. Investigation of morphological and biochemical changes of zinc oxide nanoparticles induced toxicity against multi drug resistance bacteria. J Trace Elem Med Biol. 2022; 74: 127069.

[129] Abdul—Jabbar AM, Hussian NN, Mohammed HA, Aljarbou A, Akhtar N, Khan RA. Combined Anti—Bacterial Actions of Lincomycin and Freshly Prepared Silver Nanoparticles: Overcoming the Resistance to Antibiotics and Enhancement of the Bioactivity. Antibiotics (Basel). 2022; 11: 1791.

[130] Mohammadinejat M, Sepahi AA, Alipour E. Antibacterial and Anti—Biofilm Activities of Silver Nano Particles Conjugated to Chitosan Against Multi—Drug Resistant Bacteria. Clin Lab. 2023; 69.

[131] Alqahtani FY, Aleanizy FS, Alkahtani HM, Tahir EE, Ansari SA, Alharbi A, et al. Chitosan loaded RNA polymerase inhibitor nanoparticles increased attenuation in toxin release from Streptococcus pneumonia. Saudi Pharm J. 2023; 31: 170-9.

[132] Abo—Amer AE, El—Rab SMFG, Halawani EM, Niaz AM, Bamaga MS. Prevalence and Molecular Characterization of Methicillin—Resistant Staphylococcus aureus from Nasal Specimens: Overcoming MRSA with Silver Nanoparticles and Their Applications. J Microbiol Biotechnol. 2022; 32: 1537-46.

[133] Liu B, Liu D, Chen T, Wang X, Xiang H, Wang G, et al. iTRAQ—based quantitative proteomic analysis of the antibacterial mechanism of silver nanoparticles against multidrug—resistant Streptococcus suis. Front Microbiol. 2023; 14: 1293363.

[134] Kang M, Khan F, Jo D, Oh D, Tabassum N, Kim Y. Antibiofilm and Antivirulence Activities of Gold and Zinc Oxide Nanoparticles Synthesized from Kimchi—Isolated Leuconostoc sp. Strain C2. Antibiotics (Basel). 2022; 11: 1524.

[135] Hakimov S, Kylychbekov S, Harness B, Neupane S, Hurley J, Brooks A, et al. Evaluation of silver nanoparticles attached to methylene blue as an antimicrobial agent and its cytotoxicity. Photodiagnosis Photodyn Ther. 2022; 39: 102904.

[136] Yu C, Sui S, Yu X, Huang W, Wu Y, Zeng X, et al. Ti₃C₂T_x MXene loaded with indocyanine green for synergistic photothermal and photodynamic therapy for drug—resistant bacterium. Colloids Surf B Biointerfaces. 2022; 217: 112663.

[137] Sivaraj D, Arumugam G, Kalimuthu V, Rajendran R. Enhanced anti—biofilm and biocompatibility of Zn and Mg substituted β—tricalcium phosphate/functionalized multiwalled carbon nanotube composites towards A. baumannii and Methicillin—Resistant Staphylococcus aureus, and MG—63 cells. Int J Pharm. 2022; 627: 122248.

[138] Darwish RM, Salama AH. Study the Effect of Conjugate Novel Ultra—Short Antimicrobial Peptide with Silver Nanoparticles against Methicillin Resistant S. aureus and ESBL E. coli. Antibiotics (Basel). 2022; 11: 1024.

[139] Khleifat K, Qaralleh H, Al—Limoun M, Alqaraleh M, Abu Hajleh MN, Al—Frouhk R, et al. Antibacterial Activity of Silver Nanoparticles Synthesized by Aspergillus flavus and its Synergistic Effect with Antibiotics. J Pure Appl Microbiol. 2022; 16: 1722—35.

[140] Alotaibi AM, Alsaleh NB, Aljasham AT, Tawfik EA, Almutairi MM, Assiri MA, et al. Silver Nanoparticle—Based Combinations with Antimicrobial Agents against Antimicrobial—Resistant Clinical Isolates. Antibiotics (Basel). 2022; 11: 1219.

[141] Tiri RNE, Gulbagca F, Aygun A, Cherif A, Sen F. Biosynthesis of Ag—Pt bimetallic nanoparticles using propolis extract: Antibacterial effects and catalytic activity on NaBH₄ hydrolysis. Environ Res. 2022; 206: 112622.

[142] Scandorieiro S, Rodrigues BCD, Nishio EK, Panagio LA, de Oliveira AG, Durán N, et al. Biogenic Silver Nanoparticles Strategically Combined With Origanum vulgare Derivatives: Antibacterial Mechanism of Action and Effect on Multidrug—Resistant Strains. Front Microbiol. 2022; 13: 842600.

[143] Shin J, Naskar A, Ko D, Kim S, Kim K. Bioconjugated Thymol—Zinc Oxide Nanocomposite as a Selective and Biocompatible Antibacterial Agent against Staphylococcus Species. Int J Mol Sci. 2022; 23: 6770.

[144] Mostafa EM, Abdelgawad MA, Musa A, Alotaibi NH, Elkomy MH, Ghoneim MM, et al. Chitosan Silver and Gold Nanoparticle Formation Using Endophytic Fungi as Powerful Antimicrobial and Anti—Biofilm Potentialities. Antibiotics (Basel). 2022; 11: 668.

[145] Nefedova E, Shkil N, Vazquez—Gomez RL, Garibo D, Pestryakov A, Bogdanchikova N. AgNPs Targeting the Drug Resistance Problem of Staphylococcus aureus: Susceptibility to Antibiotics and Efflux Effect. Pharmaceutics. 2022; 14: 763.

[146] Mahi Priya SR, Roselin RB, Karuppiah A, Sankar V. Formulation of Mupirocin Adsorbed Silver Nanoparticle with Antibiofilm Agents for Enhancing Antibacterial Activity. Indian J Pharm Educ Res. 2022; 56: 50-7.

[147] Al—Nemrawi NK, Alkhatib RQ, Ayyad H, Alshraiedeh N. Formulation and characterization of tobramycin—chitosan nanoparticles coated with zinc oxide nanoparticles. Saudi Pharm J. 2022; 30: 454-61.

[148] Alshammari F, Alshammari B, Moin A, Alamri A, Hagbani TA, Alobaida A, et al. Ceftriaxone Mediated Synthesized Gold Nanoparticles: A Nano—Therapeutic Tool to Target Bacterial Resistance. Pharmaceutics. 2021; 13: 1896.

[149] Malá Z, Žárská L, Bajgar R, Bogdanová K, Kolář M, Panáček A, et al. The application of antimicrobial photodynamic inactivation on methicillin—resistant S. aureus and ESBL—producing K. pneumoniae using porphyrin photosensitizer in combination with silver nanoparticles. Photodiagnosis Photodyn Ther. 2021; 33: 102140.

[150] Morshedtalab Z, Rahimi G, Emami—Nejad A, Farasat A, Mohammadbeygi A, Ghaedamini N, et al. Antibacterial Assessment of Zinc Sulfide Nanoparticles against Streptococcus pyogenes and Acinetobacter baumannii. Curr Top Med Chem. 2020; 20: 1042-55.

[151] PRISMA flow diagram [Internet]. PRISMA Executive ; c2024—2025 [cited 2025 Nov 17]. Available from: https://www.prisma—statement.org/prisma—2020—flow—diagram

[152] More PR, Pandit S, Filippis AD, Franci G, Mijakovic I, Galdiero M. Silver Nanoparticles: Bactericidal and Mechanistic Approach against Drug Resistant Pathogens. Microorganisms. 2023; 11: 369.

[153] Dube E, Okuthe GE. Silver Nanoparticle—Based Antimicrobial Coatings: Sustainable Strategies for Microbial Contamination Control. Microbiol Res. 2025; 16: 110.

[154] Chegini Z, Shariati A, Alikhani MY, Safaiee M, Rajaeih S, Arabestani M, et al. Antibacterial and antibiofilm activity of silver nanoparticles stabilized with C—phycocyanin against drug—resistant Pseudomonas aeruginosa and Staphylococcus aureus. Front Bioeng Biotechnol. 2024; 12: 1455385.

[155] Godakhindi V, Kravitz E, Vivero—Escoto JL. Light—Activable Silver Nanoparticles for Combatting Antibiotic—Resistant Bacteria and Biofilms. Molecules. 2025; 30: 626.

[156] Brown AN, Smith K, Samuels TA, Lu J, Obare SO, Scott ME. Nanoparticles functionalized with ampicillin destroy multiple—antibiotic—resistant isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and methicillin—resistant Staphylococcus aureus. Appl Environ Microbiol. 2012; 78: 2768—74.

[157] Chidhambaram N. Augmented antibacterial efficacies of the aluminium doped ZnO nanoparticles against four pathogenic bacteria. Mater Res Express. 2019; 6: 075061.

[158] Shehabeldine AM, Badr BM, Elkady FM, Watanabe T, Abdel—Maksoud MA, Alamri AM, et al. Anti—Virulence Properties of Curcumin/CuO—NPs and Their Role in Accelerating Wound Healing In Vivo. Medicina (Kaunas). 2025; 61: 515.

[159] Csakvari AC, Moisa C, Radu DG, Olariu LM, Lupitu AI, Panda AO, et al. Green Synthesis, Characterization, and Antibacterial Properties of Silver Nanoparticles Obtained by Using Diverse Varieties of Cannabis sativa Leaf Extracts. Molecules. 2021; 26: 4041.

[160] Hao Z, Wang M, Cheng L, Si M, Feng Z, Feng Z. Synergistic antibacterial mechanism of silver—copper bimetallic nanoparticles. Front Bioeng Biotechnol. 2024; 11: 1337543.

[161] Arora N, Thangavelu K, Karanikolos GN. Bimetallic Nanoparticles for Antimicrobial Applications. Front Chem. 2020; 8: 412.

[162] Ahmed OB, Alamro T. Evaluation of the antibacterial activities of face masks coated with titanium dioxide nanoparticles. Sci Rep. 2022; 12: 18739.

[163] Ghaffar I, Imran M, Perveen S, Kanwal T, Saifullah S, Bertino MF, et al. Synthesis of chitosan coated metal organic frameworks (MOFs) for increasing vancomycin bactericidal potentials against resistant S. aureus strain. Mater Sci Eng C Mater Biol Appl. 2019; 105: 110111.

[164] Pinho JO, Ferreira M, Coelho M, Pinto SN, Aguiar SI, Gaspar MM. Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin—Resistant Staphylococcus aureus Infections. Pharmaceuticals (Basel). 2024; 17: 470.

[165] Aguilar—Colomer A, Colilla M, Izquierdo—Barba I, Jiménez—Jiménez C, Mahillo I, Esteband J, et al. Impact of the antibiotic—cargo from MSNs on Gram—positive and Gram—negative bacterial biofilms. Microporous Mesoporous Mater. 2020; 311: 110681.

[166] Subramaniam S, Thomas N, Gustafsson H, Jambhrunkar M, Kidd SP, Prestidge CA. Rifampicin—Loaded Mesoporous Silica Nanoparticles for the Treatment of Intracellular Infections. Antibiotics (Basel). 2019; 8: 39.

[167] Derakhshan—Sefidi M, Bakhshi B, Rasekhi A. Thiolated chitosan nanoparticles encapsulated nisin and selenium: antimicrobial/antibiofilm/anti—attachment/immunomodulatory multi—functional agent. BMC Microbiol. 2024; 24: 257.

[168] Vanlalveni C, Lallianrawna S, Biswas A, Selvaraj M, Changmai B, Rokhum SL. Green synthesis of silver nanoparticles using plant extracts and their antimicrobial activities: a review of recent literature. RSC Adv. 2021; 11: 2804-37.

[169] Riaz M, Sharafat U, Zahid N, Ismail M, Park J, Ahmad B, et al. Synthesis of Biogenic Silver Nanocatalyst and their Antibacterial and Organic Pollutants Reduction Ability. ACS Omega. 2022; 7: 14723—34.

[170] Khan MA, Anwar MF, Ahmad M. Ocimum sanctum L water extract: In—situ green synthesis of zinc oxide nanoparticles for treatment of rheumatoid arthritis: Preclinical study. J Trace Elem Med Biol. 2023; 79: 127212.

[171] Almutairi B, Albahser G, Almeer R, Alyami NM, Almukhlafi H, Yaseen KN, et al. Investigation of Cytotoxicity Apoptotic and Inflammatory Responses of Biosynthesized Zinc Oxide Nanoparticles from Ocimum sanctum Linn in Human Skin Keratinocyte (Hacat) and Human Lung Epithelial (A549) Cells. Oxid Med Cell Longev. 2020; 2020: 1835475.

[172] Hameed S, Zhou R, Sharif S, Dharmadhikari B, Wu P, Patra P. Bioactive Gold Nanoparticles Synthesized by Lactobacillus acidophilus for Catalytic and Antibacterial Applications. ACS Appl Nano Mater. 2025; 8: 7952-66.

[173] Xiao J, Hai L, Yang K, Luo Y, Wang Z, Li J, et al. Self—enhanced ROS generation by responsive co—delivery of H₂O₂ and O₂ based on a versatile composite biomaterial for hypoxia—irrelevant multimodal antibiofilm therapy. Chem Eng J. 2023; 465: 142958.

[174] Gong X, Su L, Peng S, Xia Y, Guo J, Zou L, et al. A pH—responsive Cascade Nano—Reactor Elevates ROS Generation by Remodeling Biofilm Microenvironment for Enhanced Antibacterial Treatment. Adv Funct Mater. 2025; 35: 2425467.

[175] Ge M, Zhu W, Mei J, Hu T, Yang C, Lin H, et al. Piezoelectric—Enhanced Nanocatalysts Trigger Neutrophil N1 Polarization against Bacterial Biofilm by Disrupting Redox Homeostasis. Adv Mater. 2025; 37: e2409633.

[176] Akhtar F, Khan AU, Misba L, Akhtar K, Ali A. Antimicrobial and antibiofilm photodynamic therapy against vancomycin resistant Staphylococcus aureus (VRSA) induced infection in vitro and in vivo. Eur J Pharm Biopharm. 2021; 160: 65-76.

[177] Wang Y, Luo L, Zhang T, Hu J, Wang H, Bao F, et al. Strategically Engineered Ru(II) Complexes with Enhanced ROS Activity Enabling Potent Sonodynamic Effect against Multidrug—Resistant Biofilms. ACS Appl Mater Interfaces. 2024; 16: 52068—79.

[178] Hu X, Huang Y, Wang Y, Wang X, Hamblin MR. Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections. Front Microbiol. 2018; 9: 1299.

[179] Strengthening antimicrobial resistance national action plans through evidence [Internet]. WHO; c2025 [cited 2025 Nov 17]. Available from: https://www.who.int/news/item/14—01—2025—strengthening—antimicrobial—resistance—national—action—plans—through—evidence

[180] Naikwadi MAS, Nale GS, Masal PD, Hagawane SG, Gade OP. ICH Guidelines. Int J Multidiscip Res. 2025; 5: 7288.

[181] Sree Deepthi A, Lavanya V, Devamani K. Role Of ICH In Harmonising Drug Reulations. Int J Pharml Hcare Res. 2024; 12: 306-16.

[182] Seuba X. Chapter 15: International harmonization of pharmaceutical standards: trade, ethics and power. In: Burci GL, Toebes B, editors. Research Handbook on Global Health Law. Cheltenham: Edward Elgar Publishing; 2025. pp. 460-84.

[183] Herder M, Benavides X. ʻOur project, your problem?ʼ A case study of the WHOʼs mRNA technology transfer programme in South Africa. PLOS Glob Public Health. 2024; 4: e0003173.

[184] Parmaksiz K, Bal R, Bovenkamp Hvd, Kok MO. From promise to practice: a guide to developing pooled procurement mechanisms for medicines and vaccines. J Pharm Policy Pract. 2023; 16: 73.

[185] Vogle. ʻWe need to be part of the solutionʼ: lessons from the 2024 PPRI Conference on ensuring access to affordable medicines through innovative policies. J Pharm Policy Pract. 2024; 17: 2442002.

[186] Đorđević S, Gonzalez MM, Conejos—Sánchez I, Carreira B, Pozzi S, Acúrcio RC, et al. Current hurdles to the translation of nanomedicines from bench to the clinic. Drug Deliv Transl Res. 2022; 12: 500-25.

[187] Webb C, Forbes N, Roces CB, Anderluzzi G, Lou G, Abraham S, et al. Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP: A case study using protein—loaded liposomes. Int J Pharm. 2020; 582: 119266.

[188] Zheng C, Li M, Ding J. Challenges and Opportunities of Nanomedicines in Clinical Translation. BIO Integr. 2021; 2: 57-60.

[189] Shen Y, Gwak H, Han B. Advanced manufacturing of nanoparticle formulations of drugs and biologics using microfluidics. Analyst. 2024; 149: 614-37.

[190] Oso TA, Adebayo UO, Okesanya OJ, Chukwu CN, Ayelaagbe OB, Obadeyi KB, et al. Nanotechnology—driven antifungal strategies: A systematic review of mechanisms, therapeutic efficacy, and translational barriers in combating drug—resistant fungal infections. Next Nanotechnol. 2025; 8: 100290.

[191] Lucero—Prisno III DE, Okesanya OJ, Agboola AO, Adebayo UO, Adigun OA, Ahmed MM, et al. Emerging technologies and innovative approaches to combat antimicrobial resistance: A narrative review of next—generation therapeutic strategies. Next Bioeng. 2025; 1: 100003.

[192] Aguilar—Garay R, Lara—Ortiz LF, Campos—López M, Gonzalez—Rodriguez DE, Gamboa—Lugo MM, Mendoza—Pérez JA, et al. A Comprehensive Review of Silver and Gold Nanoparticles as Effective Antibacterial Agents. Pharmaceuticals (Basel). 2024; 17: 1134.

[193] Berini F, Orlandi V, Gornati R, Bernardini G, Marinelli F. Nanoantibiotics to fight multidrug resistant infections by Gram—positive bacteria: hope or reality? Biotechnol Adv. 2022; 57: 107948.

[194] Oso TA, Okesanya OJ, Adebayo UO, Ayelaagbe OB, Obadeyi KB, Ogunmuyiwa—James ME, et al. Harnessing nanotechnology to combat antimicrobial—resistant pathogens: a multidisciplinary approach to strengthen global public health defense systems. Beni—Suef Univ J Basic Appl Sci. 2025; 14: 119.

[195] Hetta HF, Ramadan YN, Al—Harbi AI, Ahmed EA, Battah B, Ellah NHA, et al. Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives. Biomedicines. 2023; 11: 413.

[196] Musa SS, Ibrahim AM, Alhassan MY, Musa AH, Jibo AG, Auwal AR, et al. Nanotechnology and machine learning: a promising confluence for the advancement of precision medicine. Intelligence—Based Med. 2025; 12: 100267.

[197] Balderrama—González A, Piñón—Castillo H, Ramírez—Valdespino C, Landeros—Martínez L, Orrantia—Borunda E, Esparza—Ponce H. Antimicrobial Resistance and Inorganic Nanoparticles. Int J Mol Sci. 2021; 22: 12890.

[198] Eleraky NE, Allam A, Hassan SB, Omar MM. Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations. Pharmaceutics. 2020; 12: 142.

[199] Lee N, Ko W, Hsueh P. Nanoparticles in the Treatment of Infections Caused by Multidrug—Resistant Organisms. Front Pharmacol. 2019; 10: 1153.