Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth-inhibitory effects, generally achieved by exploiting non-cisplatin-like pharmacodynamic and pharmacokinetic properties and mechanisms of action. In particular, gold(III) complexes share with platinum(II) derivatives some key chemical features, such as the preference for square-planar geometry and the typical d8 electronic configuration, making them attractive for testing as antineoplastic drugs. Moreover they have been successfully used as chemoprotectants to modulate cisplatin nephrotoxicity without decreasing its antitumor activity. In this context, we have previously reported on some gold(III)-dithiocarbamato derivatives of the type [AuIIIX2(dtc)] (X = Cl, Br; dtc = various dithiocarbamates) that reproduce very closely the main features of cisplatin. These gold(III) compounds were shown to exert outstanding in vitro cytotoxicity, even toward human tumor cell lines intrinsically resistant to cisplatin, and no cross-resistance to the reference platinum drug.[1] In order to obtain selective drug targeting to cancerous cells, peptide conjugates of Aucomplexes have been synthetized by combining different synthetic approaches (solid phase synthesis and in solution methods). The bioactive peptide selected was the octapeptide CCK8, which corresponds to the eight-residue C-terminal end of the cholecystokinin peptide hormone, and has been widely studied for its high binding affinity, in the nanomolar range, towards the two cholecystokinin receptors, CCK1-R and CCK2-R.[2] An alternative strategy to deliver anticancer drug selectively to tumor cells was the loading of the Au-complexes in supramolecular aggregates (micelles or liposomes) externally functionalized by peptides.[3]

Selective delivery of chemotherapeutics into tumor cells by use of targeting peptides

NARDON, CHIARA;
2012-01-01

Abstract

Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth-inhibitory effects, generally achieved by exploiting non-cisplatin-like pharmacodynamic and pharmacokinetic properties and mechanisms of action. In particular, gold(III) complexes share with platinum(II) derivatives some key chemical features, such as the preference for square-planar geometry and the typical d8 electronic configuration, making them attractive for testing as antineoplastic drugs. Moreover they have been successfully used as chemoprotectants to modulate cisplatin nephrotoxicity without decreasing its antitumor activity. In this context, we have previously reported on some gold(III)-dithiocarbamato derivatives of the type [AuIIIX2(dtc)] (X = Cl, Br; dtc = various dithiocarbamates) that reproduce very closely the main features of cisplatin. These gold(III) compounds were shown to exert outstanding in vitro cytotoxicity, even toward human tumor cell lines intrinsically resistant to cisplatin, and no cross-resistance to the reference platinum drug.[1] In order to obtain selective drug targeting to cancerous cells, peptide conjugates of Aucomplexes have been synthetized by combining different synthetic approaches (solid phase synthesis and in solution methods). The bioactive peptide selected was the octapeptide CCK8, which corresponds to the eight-residue C-terminal end of the cholecystokinin peptide hormone, and has been widely studied for its high binding affinity, in the nanomolar range, towards the two cholecystokinin receptors, CCK1-R and CCK2-R.[2] An alternative strategy to deliver anticancer drug selectively to tumor cells was the loading of the Au-complexes in supramolecular aggregates (micelles or liposomes) externally functionalized by peptides.[3]
drug targeting
bioactive peptide
gold(III) complexes
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1062950
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