Liệu pháp gen nhắm mục tiêu dựa trên lipoplex để ức chế sự phát triển của khối u có biểu hiện VEGFR thông qua việc sản xuất các phân tử chống sinh máu

Journal of Nanobiotechnology - 2020
Shu-Yi Ho1, Pin-Rong Chen2, Chia-Hung Chen3, Nu-Man Tsai4,5, Yu-Hsin Lin6, Chen-Si Lin7,8, Cheng-Hsun Chuang2, Xiao-Fan Huang5,9, Yi-Lin Chan10, Yen-Ku Liu2, Chen-Han Chung2,11, Shun-Long Weng12,13, Kuang-Wen Liao14,6,2,15,1
1Department of Biological Science and Technology, National Chiao Tung University, Hsinchu City, Taiwan, ROC
2Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu City, Taiwan, ROC
3Department of Medical Research, Hsinchu Mackay Memorial Hospital, Hsinchu City, Taiwan, ROC
4Department of Pathology and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City, Taiwan, ROC
5Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City, Taiwan, ROC
6Ph.D. Program in Industrial Development of College of Biological Science and Technology, National Chiao Tung University, Hsinchu City, Taiwan, ROC
7Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei City, Taiwan, ROC
8Animal Cancer Center, College of Bioresources and Agriculture, National Taiwan University, Taipei City, Taiwan, ROC
9Institute of Medicine of Chung, Shan Medical University, Taichung City, Taiwan, ROC
10Department of Life Science, Chinese Culture University, Taipei City, Taiwan, ROC
11Hank Clinic Orthopedics Surgery, Miaoli County, Taiwan, ROC
12Department of Medicine, MacKay Medical College, New Taipei City, Taiwan, ROC
13Department of Obstetrics and Gynecology, Hsinchu MacKay Memorial Hospital, Hsinchu City, Taiwan, ROC
14Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan ROC
15Center for Intelligent Drug Systems and Smart Bio-Devices, National Chiao Tung University, Hsinchu City, Taiwan, ROC

Tóm tắt

Protein fusion chống sinh máu RBDV-IgG1 Fc (RBDV), bao gồm miền liên kết thụ thể của yếu tố tăng trưởng nội mạch - A (VEGF-A), đã cho thấy tác dụng chống khối u bằng cách giảm sinh máu trong cơ thể. Nghiên cứu này đã sử dụng lipoplex cationic lipo-PEG-PEI-complex (LPPC) để đồng thời bao bọc cả protein nhắm mục tiêu RBDV và plasmid RBDV (pRBDV) mà không có liên kết cộng hóa trị nhằm đánh giá liệu pháp gen nhắm mục tiêu VEGFR ở chuột mang u ác tính (melanoma) trong cơ thể. LPPC đã bảo vệ gen liệu pháp khỏi sự phân hủy bởi DNase, và các phức hợp LPPC/RBDV có thể nhắm mục tiêu đặc hiệu vào các tế bào B16-F10 dương tính với VEGFR cả trong ống nghiệm và trong cơ thể. Dù có hay không có hướng dẫn protein nhắm mục tiêu RBDV, các protein RBDV biểu hiện từ pRBDV đều được biểu hiện và đạt nồng độ tối đa vào ngày thứ 7 trong huyết thanh sau khi truyền vào cơ thể, đồng thời gây ức chế sự phát triển đáng kể đối với khối u B16-F10 nhưng không xảy ra với các protein đối chứng IgG1. Đặc biệt, việc điều trị LPPC/pRBDV/RBDV với các phân tử nhắm mục tiêu đã làm giảm đáng kể sự phát triển khối u B16-F10 trong cơ thể, mang lại hiệu quả điều trị tốt hơn so với liệu pháp gen nhắm mục tiêu với protein IgG1 hoặc việc sử dụng thuốc protein với RBDV. Sự kết hợp đồng thời của phức hợp LPPC với liệu pháp gen pRBDV và nhắm mục tiêu protein RBDV có thể là một công cụ tiềm năng để thuận tiện triển khai liệu pháp gen nhắm mục tiêu trong điều trị ung thư.

Từ khóa

#Liệu pháp gen #RBDV #VEGFR #u ác tính #sinh máu

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