In recent years, targeted therapies have raised increasing interest as effective strategies to improve therapeutic efficiency, reduce the impact of adverse side effects, and overcome drug resistance, particularly in the field of cancer chemotherapeutics. Many examples of RGD (Arg-Gly-Asp) peptide-drug conjugates (PDCs) have been proposed as targeted drug delivery systems. These molecular hybrids embody high affinity ligands targeting disease signatures (overexpressed integrin receptors or specific integrin-related pathways within diseased cells/tissues) connected to recognized therapeutic units by means of carefully designed linker-spacer combinations, to ultimately control stability, physico-chemical properties, timing, and localization of drug release. This account has collected and critically surveyed relevant contributions from the period of 2015 to the present day, wishing to provide a window open on new synthesis strategies facing the challenging issues of site-selective drug delivery and dual drug targeting.
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