title: Drug delivery and release systems for targeted tumor therapy.
abstract: Most toxic agents currently used for chemotherapy show a narrow therapeutic window, because of their inability to distinguish between healthy and cancer cells. Targeted drug delivery offers the possibility to overcome this issue by selectively addressing structures on the surface of cancer cells, therefore reducing undesired side effects. In this broad field, peptide-drug conjugates linked by intracellular cleavable structures have evolved as highly promising agents. They can specifically deliver toxophores to tumor cells by targeting distinct receptors overexpressed in cancer. In this review, we focus on these compounds and describe important factors to develop a highly efficient peptide-drug conjugate. The necessary properties of tumor-targeting peptides are described, and the different options for cleavable linkers used to connect toxic agents and peptides are discussed, and synthetic considerations for the introduction of these structures are reported. Furthermore, recent examples and current developments of peptide-drug conjugates are critically evaluated with a special focus on the applied linker structures and their future use in cancer therapy.
authors.affiliation: Institute of Biochemistry, Universität Leipzig, Brüderstraße 34, 04103, Leipzig, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Böhme
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D003692:Delayed-Action Preparations; D004337:Drug Carriers
keywords: cancer; cleavable linker; drug delivery; peptide-drug conjugate; solid-phase peptide synthesis; targeted therapy; tumor-targeting peptide