Đánh giá hiệu quả chuyển gen trên tế bào u thần kinh đệm người của hệ vi bọt đa chức năng=Evaluation of the gene transfection efficiency on human glioma cells of the multifunctional microbubble system

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Tác giả: Khắc Cường Bùi, Thị Mai Anh Đào, Thị Hồng Nhung Dương, Văn Hiên Mai, Thị Lập Nguyễn, Xuân Bắc Nguyễn, Thị Anh Thơ Trần

Ngôn ngữ: vie

Ký hiệu phân loại:

Thông tin xuất bản: Tạp chí Y học Việt Nam (Tổng hội Y học Việt Nam), 2024

Mô tả vật lý: tr.281-289

Bộ sưu tập: Metadata

ID: 478019

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The vascular endothelial growth factor receptor 2 (VEGFR2) expression has been associated with tumor growth and aggressiveness in various cancers. VEGFR2 is highly expressed in tumor cells and endothelial cells in blood vessels that nurture brain tumors, therefore it becomes an ideal target to treat cancer. In previous studies, we have developed a novel multifunctional microbubble system, the geneloaded VEGFR2-targeted microbubble system (VCMB-pDNA), and reported that the combination of VCMB-pDNA and focus ultrasound (FUS) exposure has much greater cell-binding ability compared with other untargeted microbubbles (MBs) in vitro. In this study, the gene transfection efficiency and cell viability of the above system were evaluated on human glioma cells (U-87 MG human cell line). The results showed that the multifunctional microbubble enhanced the gene transfer efficiency by increasing the glioma cell membrane permeability, gene transfection efficiency and limiting cell death at a concentration of 4x107microbubbles per ml. We also noticed that the transfection effect varied with lipid and ligand components and that VCMB containing DPTAP and anti-VEGFR2 antibody could be the most effective tool among three types of MBs. These results suggest that combining VCMB-pDNA with FUS exposure is probably useful for efficient gene delivery and less invasive brain tumor therapeutic system.VEGFR2 là một thụ thể quan trọng trong sự tăng sinh mạch nuôi dưỡng khối u biểu hiện ở các tế bào nội mô bao quanh khối u và trên bề mặt của tế bào ung thư. Do vậy, VEGFR2 là một đích tác dụng tiềm năng chống ung thư. Từ kết quả nghiên cứu trước, nhóm nghiên cứu đã tạo được hệ vi bọt đa chức năng mang gen và kháng thể kháng VEGFR2 hướng đích tế bào u não (VCMB-pDNA) kết hợp với siêu âm tập trung (FUS) có ái lực với tế bào u thần kinh đệm lớn hơn so với các vi bọt đối chứng trên mô hình in vitro. Trong nghiên cứu này, hiệu quả chuyển gen và khả năng sống sót của hệ vi bọt trên được đánh giá trên tế bào u thần kinh đệm người (dòng tế bào U87). Kết quả cho thấy hệ vi bọt có khả năng làm tăng tính thấm màng tế bào u thần kinh đệm, tăng hiệu quả chuyển gen và hạn chế mức độ chết tế bào ở nồng độ 4x107 vi bọt/ml. Ngoài ra, hiệu quả chuyển gen thay đổi theo các thành phần lipid và phối tử trong cấu trúc vi bọt, trong đó hệ vi bọt đa chức năng (VCMB) chứa lipid DPTAP và kháng thể kháng VEGFR2 có hiệu quả chuyển gen cao nhất trong số các loại vi bọt thử nghiệm. Kết quả nghiên cứu mở ra một liệu pháp gen mới vừa tăng hiệu quả điều trị, vừa giảm tổn thương tế bào.

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