Intracellular Cargo Delivery by an Octaarginine Transporter Adapted to Target Prostate Cancer Cells through Cell Surface Protease Activation

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• 作者：Elena A. Goun ; Rajesh Shinde ; Karen W. Dehnert ; Angie Adams-Bond ; Paul A. Wender ; Christopher H. Contag ; and Benjamin L. Franc
• 刊名：Bioconjugate Chemistry
• 出版年：2006
• 出版时间：May 2006
• 年：2006
• 卷：17
• 期：3
• 页码：787 - 796
• 全文大小：215K
• 年卷期：v.17,no.3(May 2006)
• ISSN：1520-4812

文摘

Delivery of therapeutics and imaging agents to target tissues requires localization and activation strategies withmolecular specificity. Cell-associated proteases can be used for these purposes in a number of pathologic conditions,and their enzymatic activities can be exploited for activation strategies. Here, molecules based on the D-arginineoctamer (r₈) protein-transduction domain (PTD, also referred to as molecular transporters) have been adapted forselective uptake into cells only after proteolytic cleavage of a PTD-attenuating sequence by the prostate-specificantigen (PSA), an extracellular protease associated with the surface and microenvironment of certain prostatecancer cells. Convergent syntheses of these activatable PTDs (APTDs) are described, and the most effective r₈PTD-attenuating sequence is identified. The conjugates are shown to be stable in serum, cleaved by PSA, andtaken up into Jurkat (human T cells) and PC3M prostate cancer cell lines only after cleavage by PSA. TheseAPTD peptide-based molecules may facilitate targeted delivery of therapeutics or imaging agents to PSA-expressingprostate cancers.