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These SAACPs are self-assembled in water (pH 6.9) to form nanospheres with potent antibacterial activities. FEG-TEM and atomic force microscopy studies revealed the nanospherical and nanofibrillar structure. Detailed mechanistic studies probing the antibacterial activities of these self-assembled peptides substantiated that they have high efficacy to kill both Gram-positive and Gram-negative bacterial cells by permeabilizing the bacterial membranes. They exhibited potential antibacterial activity against a wide range of pathogenic non-virulent strains and clinically isolated multidrug-resistant ATCC bacterial strains. These peptide nanostructures, in particular, function as potent antibiotic sensitizers, increasing the efficacy of meropenem and reducing the minimal dosages required to stop clinical isolates that are resistant to it. MTT assay studies revealed the non-cytotoxicity of these peptides with IC50 values above 2.5 mg\/mL against human embryonic kidney (HEK-293) cell lines, which is much higher than the dose for bactericidal activity of these self-assembled peptides. This indicates that the assembled peptide nanostructures can serve as an effective scaffold in drug design, combating antimicrobial resistance with sustainable applications in nanomedicine-based therapeutics.<\/jats:p>","DOI":"10.1021\/acsabm.6c01021","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:02:13Z","timestamp":1786359733000},"page":"8169-8183","source":"Crossref","is-referenced-by-count":0,"title":["Self-Assembling Amphiphilic Cationic Peptide-Based Nanoarchitectures for Soft Biomaterials with Potential Antimicrobial Activity against Clinically Isolated Multidrug-Resistant Bacteria"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8815-8219","authenticated-orcid":true,"given":"Swapnendu","family":"Deb","sequence":"first","affiliation":[{"name":"Indian Association for the Cultivation of Science , , 2A & 2B Raja S. C. Mullick Road , , ,","place":["Jadavpur, Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4852-246X","authenticated-orcid":true,"given":"Subhecchha","family":"Baidya","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Roorkee , , , ,","place":["Haridwar, Uttarakhand, India, 247667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3074-1534","authenticated-orcid":true,"given":"Saugata","family":"Hazra","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Roorkee , , , ,","place":["Haridwar, Uttarakhand, India, 247667"]},{"name":"Indian Institute of Technology Roorkee , , , ,","place":["Haridwar, Uttarakhand, India, 247667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1309-921X","authenticated-orcid":true,"given":"Arindam","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Indian Association for the Cultivation of Science , , 2A & 2B Raja S. 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