Self-assembled peptide (CADY-1) improved the clinical application of doxorubicin.
CADY-1 is an amphipathic peptide that possesses cell-penetrating activity. As an amphipathic peptide, CADY-1 is capable of forming complexes by self-assembly, and they are these complexes that possess cell-penetrating activity. This distinct characteristic of CADY-1 makes it a potent cell-penetrating drug delivery system. Doxorubicin is a widely used cytotoxic anti-cancer drug but is limited by its toxicity. Although the liposomal formulation of doxorubicin ameliorates its toxicity, its complicated synthesis remains an obstacle to its wide clinical use. In this study, our findings revealed that CADY-1 and doxorubicin form a stable complex at optimised molar ratios in a self-assembling manner. Formation of the complex extended the blood residence time of doxorubicin in a similar fashion to that of liposomal doxorubicin. In addition, the complex was capable of carrying doxorubicin across the cell membrane, which increased the therapeutic index of doxorubicin. Experimental animals treated with a CADY-1/doxorubicin complex exhibited better tolerance and anti-tumour activity than animals treated with either liposomal doxorubicin or the free form of doxorubicin. Collectively, the findings in this study support the advantages of using complexes formed by the self-assembled peptide CADY-1 and suggest that CADY-1 is a potent drug delivery system.
Tianjin Neurological Institute, Tianjin Medical University General Hospital, China.
Ying
Y
Li
Xuemin
X
Zheng
Zhenghong
Z
Cao
Weiren
W
Xu
Jianning
J
Zhang
Min
M
Gong
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002462:Cell Membrane / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; C577078:CADY-1 peptide; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D008081:Liposomes; D010455:Peptides; D004317:Doxorubicin