Spider Silk-Based Gene Carriers for Tumor Cell-Specific Delivery

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• 作者：Keiji Numata ; Michaela R Reagan ; Robert H Goldstein ; Michael Rosenblatt ; David L Kaplan
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：August 17, 2011
• 年：2011
• 卷：22
• 期：8
• 页码：1605-1610
• 全文大小：846K
• 年卷期：v.22,no.8(August 17, 2011)
• ISSN：1520-4812

文摘

The present study demonstrates pDNA complexes of recombinant silk proteins containing poly(l-lysine) and tumor-homing peptides (THPs), which are globular and approximately 150鈥?50 nm in diameter, show significant enhancement of target specificity to tumor cells by additions of F3 and CGKRK THPs. We report herein the preparation and study of novel nanoscale silk-based ionic complexes containing pDNA able to home specifically to tumor cells. Particular focus was on how the THP, F3 (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK), and CGKRK, enhanced transfection specificity to tumor cells. Genetically engineered silk proteins containing both poly(l-lysine) domains to interact with pDNA and the THP to bind to specific tumor cells for target-specific pDNA delivery were prepared using Escherichia coli, followed by in vitro and in vivo transfection experiments into MDA-MB-435 melanoma cells and highly metastatic human breast tumor MDA-MB-231 cells. Non-tumorigenic MCF-10A breast epithelial cells were used as a control cell line for in vitro tumor-specific delivery studies. These results demonstrate that combination of the bioengineered silk delivery systems and THP can serve as a versatile and useful new platform for nonviral gene delivery.