{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:32:15Z","timestamp":1787567535810,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The development of nanoparticle (NP)-based drug delivery systems that combine passive tumor targeting, physiological stability, and therapeutic efficacy remains a key challenge in cancer nanomedicine. Here, we report a pH-responsive peptide-functionalized poly(lactic-co-glycolic acid) (PLGA) NP system designed for cancer targeting. The PLGA core is coated with a short glutamic acid\u2013lysine\u2013histidine\u2013phenylalanine x3 (EKHFFF) peptide shell, enabling tunable surface charge modulation around its isoelectric point and promoting environmental responsiveness. Physicochemical characterization confirms spherical NPs (~70\u201375 nm) with good colloidal stability, serum compatibility, and ion-dependent stability in physiological conditions. The peptide coating also provides pH-dependent modulation of the zeta potential. Evaluation of the NPs in ovarian cancer (OvCA) models, including immortalized and patient-derived cell lines (PDCLs), demonstrates efficient uptake across OvCA cell lines, with significantly enhanced internalization in PDCLs compared to immortalized cells. The EKHFFF nanoparticle (EKHFFF NP) induced minimal reactive oxygen species and nitric oxide production in macrophages, indicating low immunogenicity and favorable biocompatibility. Upon platinum loading (EKHFFF-Pt NP), the system exhibits potent cytotoxicity in both platinum-sensitive and platinum-resistant OvCA cell lines, outperforming carboplatin and showing comparable or improved efficacy relative to cisplatin in several cell lines. In vivo studies further demonstrate preferential tumor accumulation, sustained intratumoral retention, and measurable systemic circulation with a half-life of approximately 35 min.<\/jats:p>","DOI":"10.3390\/molecules31172953","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["pH-Dependent Surface Charge Modulation of Peptide-Coated Poly(lactic-co-glycolic Acid) (PLGA) Nanoparticle for Drug Delivery in Ovarian Cancer"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4486-0711","authenticated-orcid":false,"given":"Sylwia A.","family":"Dragulska","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Poursharifi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1446-3183","authenticated-orcid":false,"given":"Benjamin","family":"Lesea-Pringle","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0883-331X","authenticated-orcid":false,"given":"Maxier","family":"Acosta Santiago","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Mayes","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-4761","authenticated-orcid":false,"given":"Maria","family":"Padron-Rhenals","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Catalina","family":"Camacho","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Engelman","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Camacho-Vanegas","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Martignetti","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA"},{"name":"Women\u2019s Health Research Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl., New York, NY 10029, USA"},{"name":"Rudy Ruggles Research Institute, Western Connecticut Health Network, 131 West St., Danbury, CT 06810, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta J.","family":"Mieszawska","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125555","DOI":"10.1016\/j.ijpharm.2025.125555","article-title":"Focus on therapeutic peptides and their delivery","volume":"675","author":"Rosson","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rossino, G., Marchese, E., Galli, G., Verde, F., Finizio, M., Serra, M., Linciano, P., and Collina, S. (2023). 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