{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:19:20Z","timestamp":1785424760235,"version":"3.56.0"},"reference-count":166,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'universit\u00e0 e della ricerca","doi-asserted-by":"crossref","award":["2022MBK24T"],"award-info":[{"award-number":["2022MBK24T"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2022MBK24T"],"award-info":[{"award-number":["2022MBK24T"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Metal-based anticancer drugs, particularly platinum and gold complexes, play a central role in chemotherapy but are often limited by systemic toxicity, resistance, and suboptimal selectivity. Peptide conjugation has emerged as a versatile strategy to modulate the pharmacokinetic and biological properties of metal complexes, enabling targeted delivery, improved uptake, and controlled activation. This review aims to critically analyze platinum- and gold-peptide bioconjugates in cancer therapy, focusing on directly reactive metal complexes and redox-activated prodrug systems. Methods: Relevant literature from the past two decades was surveyed across major scientific databases, focusing on the design, conjugation strategies, biological activity, and mechanisms of action of Pt- and Au-peptide bioconjugates. Results: Reviewed studies reveal distinct behavior for platinum- and gold-based systems. Pt(II)-peptide conjugates primarily retain DNA-reactive interaction, with peptides mainly enhancing cellular uptake, selective targeting and solubility, although improved cytotoxicity is not consistently achieved. In contrast, Pt(IV)-peptide conjugates function as prodrugs, where axial peptide functionalization allows greater structural versatility and sometimes improved selectivity, with therapeutic efficacy strongly depending on intracellular reduction kinetics. Au(I)-peptide conjugates act as directly reactive species targeting thiol- and selenol-containing proteins, whereas Au(III) bioconjugates often behave as redox-activated prodrugs, with peptide conjugation influencing stability and cellular fate. Conclusions: Overall, peptide conjugation represents a powerful but non-trivial approach for optimizing metal-based anticancer agents. The success of metal-peptide bioconjugates critically depends on balancing peptide-mediated delivery with the intrinsic reactivity and activation pathways of the metal center. A function-guided design of bioconjugates is essential to achieve genuine selectivity and therapeutic benefit.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070794","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gold- and Platinum-Peptide Bioconjugates in Cancer Therapy: Recent Advances and Future Directions"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5099-6967","authenticated-orcid":false,"given":"Anna","family":"Giorgio","sequence":"first","affiliation":[{"name":"Institute of Biostructure and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy"},{"name":"Interuniversity Research Centre on Bioactive Peptides (CIRPeB) \u201cCarlo Pedone\u201d, University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Abagnale","sequence":"additional","affiliation":[{"name":"Institute of Biostructure and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy"},{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania \u201cL. Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5086-2459","authenticated-orcid":false,"given":"Michele","family":"Saviano","sequence":"additional","affiliation":[{"name":"Institute of Crystallography (IC), CNR, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-8635","authenticated-orcid":false,"given":"Annarita","family":"Del Gatto","sequence":"additional","affiliation":[{"name":"Institute of Biostructure and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy"},{"name":"Interuniversity Research Centre on Bioactive Peptides (CIRPeB) \u201cCarlo Pedone\u201d, University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6843-0152","authenticated-orcid":false,"given":"Laura","family":"Zaccaro","sequence":"additional","affiliation":[{"name":"Institute of Biostructure and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy"},{"name":"Interuniversity Research Centre on Bioactive Peptides (CIRPeB) \u201cCarlo Pedone\u201d, University of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lippert, B. 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