Immuno-chemotherapeutic platinum(IV) prodrugs of cisplatin as multimodal anticancer agents.
There is growing consensus that the clinical therapeutic efficacy of some chemotherapeutic agents depends on their off-target immune-modulating effects. Pt anticancer drugs have previously been identified to be potent immunomodulators of both the innate and the adaptive immune system. Nevertheless, there has been little development in the rational design of Pt-based chemotherapeutic agents to exploit their immune-activating capabilities. The FPR1/2 formyl peptide receptors are highly expressed in immune cells, as well as in many metastatic cancers. Herein, we report a rationally designed multimodal Pt(IV) prodrug containing a FPR1/2-targeting peptide that combines chemotherapy with immunotherapy to achieve therapeutic synergy and demonstrate the feasibility of this approach.
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore (Singapore).
Daniel Yuan Qiang
DY
Wong
Charmian Hui Fang
CH
Yeo
Wee Han
WH
Ang
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry* / Q000633:toxicity; D056831:Coordination Complexes / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D061986:MCF-7 Cells; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D010984:Platinum / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry* / Q000633:toxicity; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D056831:Coordination Complexes; C469986:FPR1 protein, human; C105101:FPR2 protein, human; D011355:Prodrugs; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D010984:Platinum; D002945:Cisplatin
antitumor agents; cisplatin; drug targeting; peptides; platinum