{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:03:23Z","timestamp":1794002603712,"version":"4.8.0"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The growing challenge of antimicrobial resistance to antibiotics requires  novel synthetic drugs or new formulations for old drugs. Here, cationic nanostructured particles (NPs) self-assembled from cationic bilayer fragments and polyelectrolytes  are tested against four multidrug-resistant (MDR) strains of clinical importance. The  non-hemolytic poly(diallyldimethylammonium) chloride (PDDA) polymer as the outer NP layer shows a remarkable activity against these organisms. The mechanism of cell death involves bacterial membrane lysis as determined from the leakage of inner phosphorylated compounds and possibly disassembly of the NP with the appearance of multilayered fibers made of the NP components and the biopolymers withdrawn from the cell wall. The NPs display broad-spectrum activity against MDR microorganisms, including Gram-negative and Gram-positive bacteria and yeast.<\/jats:p>","DOI":"10.3390\/ijms16036337","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T10:38:57Z","timestamp":1426761537000},"page":"6337-6352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Supramolecular Cationic Assemblies against  Multidrug-Resistant Microorganisms:  Activity and Mechanism of Action"],"prefix":"10.3390","volume":"16","author":[{"given":"Let\u00edcia","family":"De Melo Carrasco","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo,  Caixa Postal 26077, CEP 05513-970 S\u00e3o Paulo, Brazil"},{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Ci\u00eancias Farmac\u00eauticas, Universidade de S\u00e3o Paulo, CEP 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Ci\u00eancias Farmac\u00eauticas, Universidade de S\u00e3o Paulo, CEP 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-2707","authenticated-orcid":false,"given":"Ana","family":"Carmona-Ribeiro","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo,  Caixa Postal 26077, CEP 05513-970 S\u00e3o Paulo, Brazil"},{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Ci\u00eancias Farmac\u00eauticas, Universidade de S\u00e3o Paulo, CEP 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrd4363","article-title":"Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies","volume":"13","author":"Mitragotri","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1517\/17425247.2014.917076","article-title":"Development and optimization of curcumin-loaded mannosylated chitosan nanoparticles using response surface methodology in the treatment of visceral leishmaniasis","volume":"11","author":"Chaubey","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1021\/bc400210x","article-title":"Novel isoprenoyl nanoassembled prodrug for Paclitaxel delivery","volume":"24","author":"Mura","year":"2013","journal-title":"Bioconjug. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"904","DOI":"10.3109\/1061186X.2013.837469","article-title":"Nanotechnology in cancer therapy","volume":"21","author":"Aslan","year":"2013","journal-title":"J. Drug Target."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cis.2013.11.007","article-title":"Antimicrobial polymer nanostructures: Synthetic route, mechanism of action and perspective","volume":"203","author":"Song","year":"2014","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1271\/bbb.70.1060","article-title":"Antibiotic resistance in bacteria and its future for novel antibiotic development","volume":"70","author":"Yoneyama","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0196-6553(99)70056-8","article-title":"Bacterial resistance and topical antimicrobial wash products","volume":"27","author":"Jones","year":"1999","journal-title":"Am. J. Infect. Control"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55S","DOI":"10.1046\/j.1365-2672.92.5s1.8.x","article-title":"Mechanisms of bacterial biocide and antibiotic resistance","volume":"92","author":"Poole","year":"2002","journal-title":"J. Appl. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/S1473-3099(03)00833-8","article-title":"Biocide use and antibiotic resistance: The relevance of laboratory findings to clinical and environmental situations","volume":"3","author":"Russell","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9906","DOI":"10.3390\/ijms14059906","article-title":"Cationic antimicrobial polymers and their assemblies","volume":"14","author":"Carrasco","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1128\/AAC.03305-14","article-title":"Cationic liposomal sodium stibogluconate (SSG), a potent therapeutic tool for treatment of infection by SSG-sensitive and -resistant Leishmania donovani","volume":"59","author":"Sinha","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18040","DOI":"10.3390\/ijms151018040","article-title":"Novel formulations for antimicrobial peptides","volume":"15","author":"Carrasco","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1055\/s-0028-1129654","article-title":"Eineneueklasse von disinfektionsmitteln","volume":"61","author":"Domagk","year":"1935","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1021\/bm060476w","article-title":"Surface-active antifungal polyquaternary amine","volume":"7","author":"Ravikumar","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1021\/bm070353r","article-title":"From multifunctionalized poly(ethylene imine)s toward antimicrobial coatings","volume":"8","author":"Pasquier","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12300","DOI":"10.1021\/la101500s","article-title":"Antimicrobial particles from cationic lipid and polyelectrolytes","volume":"26","author":"Melo","year":"2010","journal-title":"Langmuir"},{"key":"ref_17","first-page":"350","article-title":"Fungicidal nanoparticles of low toxicity from cationic lipid and polyelectrolytes","volume":"3","author":"Melo","year":"2012","journal-title":"NSTI Nanotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1166\/jbn.2015.1962","article-title":"Nanocomposite hydrogels and their applications in drug delivery and tissue engineering","volume":"11","author":"Song","year":"2015","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41496","DOI":"10.1002\/app.41496","article-title":"Construction of lysozyme exfoliated rectorite-based electrospun nanofibrous membranes for bacterial inhibition","volume":"132","author":"Zhan","year":"2015","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9477","DOI":"10.1039\/C4NR02814G","article-title":"Emerging chitin and chitosan nanofibrous materials for biomedical applications","volume":"6","author":"Ding","year":"2014","journal-title":"Nanoscale"},{"key":"ref_21","first-page":"25:1","article-title":"Fungicidal assemblies and their mode of action","volume":"2","author":"Carrasco","year":"2013","journal-title":"OA Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6:1","DOI":"10.1186\/1477-3155-6-6","article-title":"Cationic nanoparticles for delivery of amphotericin B: Preparation, characterization and activity in vitro","volume":"6","author":"Vieira","year":"2008","journal-title":"J. Nanobiotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.2174\/092986706776872925","article-title":"Lipid bilayer fragments and disks in drug delivery","volume":"13","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_24","first-page":"249","article-title":"Biomimetic nanoparticles: Preparation, characterization and biomedical applications","volume":"5","year":"2010","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/0040-6090(92)90417-A","article-title":"Buildup of ultrathin multilayer films by a self-assembly process: III. Consecutively alternating adsorption of anionic and cationic polyelectrolytes on charged surfaces","volume":"210\u2013211","author":"Decher","year":"1992","journal-title":"Thin Solid Films"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/978-1-61779-953-2_22","article-title":"Preparation and characterization of biomimetic nanoparticles for drug delivery","volume":"906","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1021\/la970353k","article-title":"Cationic vesicles as bactericides","volume":"13","author":"Martins","year":"1997","journal-title":"Langmuir"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/S0022-2275(20)33392-7","article-title":"Interactions between cationic liposomes and bacteria: The physical-chemistry of the bactericidal action","volume":"40","author":"Mamizuka","year":"1999","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8230","DOI":"10.1021\/jp003315+","article-title":"Interactions between cationic vesicles and Candida albicans","volume":"105","author":"Mamizuka","year":"2001","journal-title":"J. Phys. Chem. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1021\/am200150t","article-title":"Structure-activity relationship for quaternary ammonium compounds hybridized with poly (methyl methacrylate)","volume":"3","author":"Melo","year":"2011","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40:1","DOI":"10.1186\/1472-6750-11-40","article-title":"Supramolecular assemblies of rifampicin and cationic bilayers: Preparation, characterization and micobactericidal activity","volume":"11","author":"Barbassa","year":"2011","journal-title":"BMC Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9677","DOI":"10.1021\/la401527j","article-title":"Antimicrobial particles from emulsion polymerization of methyl methacrylate in the presence of quaternary ammonium surfactants","volume":"29","author":"Naves","year":"2013","journal-title":"Langmuir"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1136\/jcp.32.4.382","article-title":"Limits to progressive reduction of resident skin bacteria by disinfection","volume":"32","author":"Lilly","year":"1979","journal-title":"J. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e61964","DOI":"10.1371\/journal.pone.0061964","article-title":"Chicken cathelicidins display antimicrobial activity against multiresistant bacteria without inducing strong resistance","volume":"8","author":"Veldhuizen","year":"2013","journal-title":"PLoS One"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nrmicro2182","article-title":"Staphylococcus epidermidis\u2014The \u201caccidental\u201d pathogen","volume":"7","author":"Otto","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/1011-1344(95)07147-4","article-title":"Meso-substituted cationic porphyrins as efficient photosensitizers of gram-positive and gram-negative bacteria","volume":"32","author":"Merchat","year":"1996","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1751-1097.1992.tb04213.x","article-title":"Inactivation of gram-negative bacteria by photosensitized porphyrins","volume":"55","author":"Nitzan","year":"1992","journal-title":"Photochem. Photobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1085\/jgp.52.1.227","article-title":"Lytic agents, cell permeability and monolayer penetrability","volume":"52","author":"Salton","year":"1968","journal-title":"J. Gen. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0964-8305(96)00015-7","article-title":"Mechanisms of action of antibacterial biocides","volume":"36","author":"Denyer","year":"1995","journal-title":"Int. Biodeterior. Biodegrad."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e92723","DOI":"10.1371\/journal.pone.0092723","article-title":"Underlying mechanism of antimicrobial activity of chitosan microparticles and implications for the treatment of infectious diseases","volume":"9","author":"Jeon","year":"2014","journal-title":"PLoS One"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1021\/bm0701088","article-title":"Antibacterial activities of poly (amidoamine) dendrimers terminated with amino and poly (ethylene glycol) groups","volume":"8","author":"Calabretta","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1166\/jbn.2007.047","article-title":"The effect of polyamidoamine dendrimers on the in vitro cytotoxicity of paclitaxel in cultured prostate cancer (PC-3M) cells","volume":"3","author":"Devarakonda","year":"2007","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.3390\/polym3031199","article-title":"Dark antimicrobial mechanisms of cationic phenylene ethynylene polymers and oligomers against Escherichia coli","volume":"3","author":"Wang","year":"2011","journal-title":"Polymers"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8907","DOI":"10.1016\/j.biomaterials.2012.08.046","article-title":"Arginine-rich self-assembling peptides as potent antibacterial gels","volume":"33","author":"Veiga","year":"2012","journal-title":"Biomaterials"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.cocis.2010.05.006","article-title":"Interaction between amphiphilic peptides and phospholipid membranes","volume":"15","author":"Ringstad","year":"2010","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3109\/07388551.2011.594423","article-title":"Antimicrobial peptides: Key components of the innate immune system","volume":"32","author":"Pasupuleti","year":"2012","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_47","first-page":"37","article-title":"Bacteria-removing and bactericidal efficiencies of pdadmac composite coagulants in enhanced coagulation treatment","volume":"41","author":"Zhao","year":"2013","journal-title":"Clean"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1021\/la00008a024","article-title":"Bacteria flocculation and death by cationic vesicles","volume":"11","author":"Sicchierolli","year":"1995","journal-title":"Langmuir"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5981","DOI":"10.1073\/pnas.111143098","article-title":"Designing surfaces that kill bacteria on contact","volume":"98","author":"Tiller","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/bit.20454","article-title":"Immobilized N-alkylated polyethylenimine avidly kills bacteria by rupturing cell membranes with no resistance developed","volume":"90","author":"Milovic","year":"2005","journal-title":"Biotechnol. Bioeng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nmat2915","article-title":"A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability","volume":"10","author":"Li","year":"2011","journal-title":"Nat. Mater."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature14098","article-title":"A new antibiotic kills pathogens without detectable resistance","volume":"517","author":"Ling","year":"2015","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/rb\/rbu016","article-title":"Functionalized scaffolds to enhance tissue regeneration","volume":"2","author":"Guo","year":"2015","journal-title":"Regen. Biomater."},{"key":"ref_54","first-page":"11","article-title":"Antimicrobial peptide resistance mechanisms of human bacterial pathogens","volume":"8","author":"Nizet","year":"2006","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0167-7799(00)89017-4","article-title":"Engineering liposomes for drug delivery: Progress and problems","volume":"13","author":"Gregoriadis","year":"1995","journal-title":"Trends Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/jac\/dkg383","article-title":"In vivo activity of a novel amphotericin B formulation with synthetic cationic bilayer fragments","volume":"52","author":"Lincopan","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1016\/j.vaccine.2009.07.066","article-title":"Novel immunoadjuvants based on cationic lipid: Preparation, characterization and activity in vivo","volume":"27","author":"Lincopan","year":"2009","journal-title":"Vaccine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jconrel.2011.10.017","article-title":"Stable assemblies of cationic bilayer fragments and CpG oligonucleotide with enhanced immunoadjuvant activity in vivo","volume":"160","author":"Rozenfeld","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Duc, G.H.T. (2014). Immune Response Activation, InTech. [1st ed.].","DOI":"10.5772\/57004"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6077","DOI":"10.1021\/la980345j","article-title":"Interactions between cationic vesicles and serum proteins","volume":"14","author":"Carvalho","year":"1998","journal-title":"Langmuir"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1039\/cs9922100209","article-title":"Synthetic amphiphile vesicles","volume":"21","year":"1992","journal-title":"Chem. Soc. Rev."},{"key":"ref_62","unstructured":"Dahneke, B. (1983). Measurements of Suspended Particles by Quasielastic Light Scattering, Wiley-Interscience."},{"key":"ref_63","unstructured":"Murray, P.R., Baron, E.J., Jorgensen, J.H., Landry, M.L., and Pfaller, M.A. (2007). Manual of Clinical Microbiology, ASM Press. [9th ed.]."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"12225","DOI":"10.1021\/la302303d","article-title":"Cleavable cationic antibacterial amphiphiles: Synthesis, mechanism of action, and cytotoxicities","volume":"28","author":"Hoque","year":"2012","journal-title":"Langmuir"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/3\/6337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:43:41Z","timestamp":1760215421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/3\/6337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,19]]},"references-count":64,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3]]}},"alternative-id":["ijms16036337"],"URL":"https:\/\/doi.org\/10.3390\/ijms16036337","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,19]]}}}