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      Advancing Nanotechnology: Targeting Biofilm-Forming Bacteria with Antimicrobial Peptides

      review-article
      1 , 1 , 2 , * , , 3 , * , , 1 , * ,
      BME Frontiers
      AAAS

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          Abstract

          Nanotechnology offers innovative solutions for addressing the challenges posed by biofilm-forming bacteria, which are highly resistant to conventional antimicrobial therapies. This review explores the integration of pharmaceutical nanotechnology with antimicrobial peptides (AMPs) to enhance the treatment of biofilm-related infections. The use of various nanoparticle systems—including inorganic/metallic, polymeric, lipid-based, and dendrimer nanostructures—provides promising avenues for improving drug delivery, targeting, and biofilm disruption. These nanocarriers facilitate the penetration of biofilms, down-regulate biofilm-associated genes, such as ALS1, ALS3, EFG1, and HWP1, and inhibit bacterial defense mechanisms through membrane disruption, reactive oxygen species generation, and intracellular targeting. Furthermore, nanoparticle formulations such as NZ2114-NPs demonstrate enhanced efficacy by reducing biofilm bacterial counts by several orders of magnitude. This review highlights the potential of combining nanotechnology with AMPs to create novel, targeted therapeutic approaches for combatting biofilm-related infections and overcoming the limitations of traditional antimicrobial treatments.

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          Most cited references113

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          Targeting microbial biofilms: current and prospective therapeutic strategies.

          Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections. The multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials and indicates the need for multi-targeted or combinatorial therapies. In this Review, we focus on current therapeutic strategies and those under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by in vivo or ex vivo studies, highlight emerging biofilm-targeting technologies and provide a rationale for multi-targeted therapies aimed at disrupting the complex biofilm microenvironment.
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            Metal-Based Nanoparticles as Antimicrobial Agents: An Overview

            Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.
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              Polymeric Nanoparticles: Production, Characterization, Toxicology and Ecotoxicology

              Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.
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                Author and article information

                Journal
                BME Front
                BME Front
                BMEF
                BME Frontiers
                AAAS
                2765-8031
                04 March 2025
                2025
                : 6
                : 0104
                Affiliations
                [ 1 ] São Paulo State University (UNESP) , Tuberculosis Research Laboratory, School of Pharmaceutical Sciences, Araraquara, Brazil.
                [ 2 ]Facultad de Ciencias de la Universidad Nacional de Ingeniería, Lima, Peru.
                [ 3 ] Vicerrectorado de Investigación, Universidad Católica de Santa María de Arequipa , Arequipa 04000, Peru.
                Author notes
                [*] [* ]Address correspondence to: roqueb.cesar@ 123456gmail.com (C.A.R.-B.); fernando.pavan@ 123456unesp.br (F.R.P.); Christian.carnero.c@ 123456uni.pe (C.S.C.C.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-9262-0383
                Article
                0104
                10.34133/bmef.0104
                11876546
                40041091
                ebcad7f6-fe16-4948-b87d-8d11bb2b5e43
                Copyright © 2025 Julia Valladares Campos et al.

                Exclusive licensee Suzhou Institute of Biomedical Engineering and Technology, CAS. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License (CC BY 4.0).

                History
                : 19 November 2024
                : 21 January 2025
                : 07 February 2025
                : 04 March 2025
                Page count
                Figures: 5, Tables: 3, References: 122, Pages: 0
                Categories
                Review Article

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