Targeting prostate cancer cells with genetically engineered polypeptide-based micelles displaying gastrin-releasing peptide

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• 作者：Wei Zhang^a ; Sanjay Garg^a ; Preethi Eldi^a ; Fiona Huan-huan Zhou^b ; Ian R.D. Johnson^a ; Doug A. Brooks^a ; Frankie Lam^a ; Grigori Rychkov^b ; John Hayball^a ; Hugo Albrecht^a ; ^{hugo.albrecht@unisa.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：G protein-coupled receptors (GPCRs) ; Elastin-like polypeptide (ELP) ; Gastrin releasing peptide (GRP) ; Micelle ; Prostate cancer
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 November 2016
• 年：2016
• 卷：513
• 期：1-2
• 页码：270-279
• 全文大小：2505 K

文摘

In recent years G protein-coupled receptors (GPCRs) have emerged as crucial tumorigenic factors that drive aberrant cancer growth, metastasis and angiogenesis. Consequently, a number of GPCRs are strongly expressed in cancer derived cell lines and tissue samples. Therefore a rational anti-cancer strategy is the design of nano-medicines that specifically target GPCRs to bind and internalise cytotoxic drugs into cancer cells. Herein, we report the genetic engineering of a self-assembling nanoparticle based on elastin-like polypeptide (ELP), which has been fused with gastrin releasing peptide (GRP). These nanoparticles increased intracellular calcium concentrations when added to GRP receptor positive PC-3 prostate cancer cells, demonstrating specific receptor activation. Moreover, GRP-displaying fluorescent labelled nanoparticles showed specific cell-surface interaction with PC-3 prostate cancer cells and increased endocytic uptake. These nanoparticles therefore provide a targeted molecular carrier system for evaluating the delivery of cytotoxic drugs into cancer cells.