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Conjugating chemotherapeutic metallodrugs to glucose-mimicking glycoconjugates supports tumor-selective intracellular delivery. Glycosylated metal scaffolds are also extended to imaging and antiviral, antimicrobial, antiparasitic, and anti-neurodegenerative applications, and the review critically summarizes recent design advances beyond the authors’ 2015 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are glucose transporters (GLUTs) important for tumor-targeted metallodrugs?","Question",{"text":63,"@type":64},"Tumor cells increase glucose uptake by overexpressing GLUTs, which enhances internal delivery opportunities for glucose-mimicking drug conjugates.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What is the Warburg effect and how does it relate to medicinal glyco-metallodrugs?",{"text":68,"@type":64},"The Warburg effect refers to predominant aerobic glycolysis in tumor tissues even under sufficient oxygen, supporting the rationale to exploit glucose metabolism for targeted delivery.",{"name":70,"@type":61,"acceptedAnswer":71},"Besides cancer therapy, what other medical uses are mentioned for glycosylated metal scaffolds?",{"text":72,"@type":64},"The text highlights potential roles in tumor imaging and in antiviral, antimicrobial, antiparasitic, and anti-neurodegenerative 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Ioannis Titilas , Simona Cacciapuoti and Luca Ronconi *  \nAcademic Editors: Giulia Bononi and Carlotta Granchi  \nReceived: 20 July 2025  \nRevised: 25 August 2025  \nAccepted: 27 August 2025  \nPublished: 29 August 2025  \nCitation: Brescia, F.; Titilas, I.; Cacciapuoti, S.; Ronconi, L. Recent Advances in the Development of Metal-Glycoconjugates for Medicinal Applications. Molecules 2025, 30, 3537 .  \n[https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules30173537  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \nSchool of Biological and Chemical Sciences, University of Galway, University Road, H91 TK33 Galway, Ireland; [f.brescia1@universityofgalway.ie](f.brescia1@universityofgalway.ie) (F.B.); [john351990@hotmail.com](john351990@hotmail.com) (I.T.);  \n[simona.cacciapuoti@universityofgalway.ie](simona.cacciapuoti@universityofgalway.ie) (S.C.)  \n* Correspondence: [luca.ronconi@universityofgalway.ie](luca.ronconi@universityofgalway.ie)  \nAbstract  \nRapidly proliferating tumor cells exhibit elevated demands for nutrients and energy to support their uncontrolled growth, with glucose serving as a key metabolic substrate. Glucose is transported into cells via facilitated diffusion mediated by glucose transporters (GLUTs), after which it undergoes a series of enzymatic reactions to generate energy. To accommodate their heightened metabolic needs, cancer cells frequently overexpress GLUTs, thereby enhancing glucose uptake. Notably, aerobic glycolysis—commonly referred to as the “Warburg effect”—has been identified as the predominant pathway of glucose metabolism within tumor tissues, even in the presence of adequate oxygen levels. Consequently, the conjugation of chemotherapeutic agents, including metallodrugs, to glucose-mimicking substrates holds significant potential for achieving tumor-specific intracellular drug delivery by exploiting the elevated glucose uptake characteristic of cancer cells. Moreover, in recent years, glycosylation of metal scaffolds has been extended to the development of bioactive metallodrugs for applications other than cancer treatment, such as potential tumor imaging, antiviral, antimicrobial, antiparasitic and anti-neurodegenerative agents. Accordingly, major advancements in the design of metal-based glycoconjugates for medicinal applications are here summarized and critically discussed, focusing on related results and discoveries published subsequently to our previous (2015) review article on the topic.  \nKeywords: glycoconjugates; metallodrugs; tumor metabolism; Warburg effect; targeted anticancer chemotherapy; chemotherapeutics; tumor imaging; antivirals; antimicrobials  \n1. Introduction  \nOver the last 60 years, metal complexes have increasingly taken on a central role in medicinal chemistry, demonstrating unique properties, ranging from the ability to bind DNA and modulate metabolic pathways to the controlled production of reactive oxygen species (ROS), for therapeutic and diagnostic applications [1] . Thanks to their varied coordination geometries, accessibility to multiple oxidation states, and tunable physico-chemical (including photophysical) features, metal ions allow for the design of molecules with high specificity for biological targets, multi-level mechanisms of action, and pharmacokinetic profiles that are unlikely to be achieved with “purely organic” species. In particular, the integration of appropriately chosen ligands allows the modulation of lipophilicity, tissue selectivity, and release kinetics, thus providing a rational optimization opportunity that h","cbCaiclFw8rkyiFn","https://ap.wps.com/l/cbCaiclFw8rkyiFn","pdf",5967346,47,"English","# Abstract\n# Introduction","[{\"question\":\"Why are glucose transporters (GLUTs) important for tumor-targeted metallodrugs?\",\"answer\":\"Tumor cells increase glucose uptake by overexpressing GLUTs, which enhances internal delivery opportunities for glucose-mimicking drug conjugates.\"},{\"question\":\"What is the Warburg effect and how does it relate to medicinal glyco-metallodrugs?\",\"answer\":\"The Warburg effect refers to predominant aerobic glycolysis in tumor tissues even under sufficient oxygen, supporting the rationale to exploit glucose metabolism for targeted delivery.\"},{\"question\":\"Besides cancer therapy, what other medical uses are mentioned for glycosylated metal scaffolds?\",\"answer\":\"The text highlights potential roles in tumor imaging and in antiviral, antimicrobial, antiparasitic, and anti-neurodegenerative applications.\"}]","Recent Advances in the Development of Metal-Glycoconjugates for Medicinal Applications | PDF",1790200245,118]