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首页> 外文期刊>Journal of drug targeting >VPAC receptor mediated tumor cell targeting by protamine based nanoparticles.
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VPAC receptor mediated tumor cell targeting by protamine based nanoparticles.

机译:VPAC受体介导的基于鱼精蛋白的纳米颗粒靶向肿瘤细胞。

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摘要

The receptors for vasoactive intestinal peptide (VIP), VPAC1-, VPAC2-, and PAC1-receptor are overexpressed by various tumor cells. VIP can target these receptors and transport conjugates into the cell. However, the use of VIP for tumor cell targeting is hampered by the peptides short half-lives due to enzymatic degradation. Because protamine-based nanoparticles (proticles) protect the peptide and serve as peptide depot, we explored the potential of proticles as carrier for VIP-conjugated molecules. The VIP-loaded proticles were stable as shown by Fluorescence Correlation Spectroscopy. With Confocal Laser Scanning Microscopy, we observed VIP-loaded proticles to specifically target the tumor cells. The cell binding triggered the substance release and conjugate internalization of VIP-Cy3 in vitro and ex vivo by human tumors. We observed VIP releasing proticle depots distributed in rat tissue and human tumors. Our findings warrant further studies to explore the proticles potential to enable peptide-mediated targeting for in vivo and clinical applications.
机译:血管活性肠肽(VIP),VPAC1-,VPAC2-和PAC1-受体的受体被各种肿瘤细胞过度表达。 VIP可以靶向这些受体并将结合物转运到细胞中。然而,由于酶促降解,肽的短半衰期阻碍了将VIP用于肿瘤细胞靶向。由于基于鱼精蛋白的纳米颗粒(质子)可以保护肽并充当肽仓库,因此我们探索了质子作为VIP连接分子载体的潜力。如荧光相关光谱法所示,加载VIP的质子是稳定的。使用共聚焦激光扫描显微镜,我们观察到加载VIP的质子特异性靶向肿瘤细胞。细胞结合触发了人肿瘤在体外和离体的物质释放和VIP-Cy3的缀合物内在化。我们观察到VIP释放质子贮库分布在大鼠组织和人类肿瘤中。我们的发现值得进一步研究,以探索能够在体内和临床应用中实现肽介导的靶向的质子潜力。

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