Improved therapeutic efficacy of doxorubicin through conjugation with a novel peptide drug delivery technology (Vectocell)

被引：44

作者：

Meyer-Losic, Florence ^{[1
]}

Quinonero, Jerome ^{[1
]}

Dubois, Vincent ^{[1
]}

Alluis, Bertrand ^{[1
]}

Dechambre, Mireille ^{[1
]}

Michel, Matthieu ^{[1
]}

Cailler, Francoise ^{[1
]}

Fernandez, Anne-Marie ^{[1
]}

Trouet, Andre ^{[1
]}

Kearsey, Jonathan ^{[1
]}

机构：

[1] Diatos SA, F-75014 Paris, France

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 23期

关键词：

D O I：

10.1021/jm0606591

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short ( 15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attractive candidates to minimize many of the limitations observed for a broad range of cytotoxic molecules. The studies reported here characterized the in vitro and in vivo efficacy of a range of Vectocell peptides conjugated to doxorubicin through different linkers. These studies show that the in vivo therapeutic index of doxorubicin can be improved by conjugation with a specific Vectocell peptide ( DPV1047) through an ester linker to C14 of doxorubicin, in both colon and breast tumor models. This conjugate was also shown to have significant in vivo antitumoral activity in a model resistant to doxorubicin, suggesting that this conjugate is able to circumvent the multidrug resistance ( MDR) phenotype. These experiments therefore provide support for the use of the Vectocell technology with other cytotoxic agents.

引用

页码：6908 / 6916

页数：9

共 26 条

[1]

Efficient gene delivery by a peptide derived from a monoclonal anti-DNA antibody [J].