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

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Meyer-Losic F,Quinonero J,Dubois V,Alluis B,Dechambre M,Michel M,Cailler F,Fernandez AM,Trouet A,Kearsey J

doi

10.1021/jm0606591

subject

Has Abstract

pub_date

2006-11-16 00:00:00

pages

6908-16

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

49

pub_type

杂志文章

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