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Giao hàng có chọn lọc siRNA bằng cách sử dụng lipoplex liên hợp transferrin tăng cường tính nhạy cảm của các tế bào ác tính có biểu hiện cao CD71 với sự tấn công bổ sung do kháng thể trung gian
Tóm tắt
Việc biểu hiện quá mức các protein điều hòa bổ sung liên kết với màng (mCRP; CD46, CD55, CD59) ngăn cản quá trình opson hóa và độc tính phụ thuộc vào bổ sung (CDC) được coi là một trở ngại lớn cho liệu pháp miễn dịch ung thư dựa trên kháng thể thành công. Để tránh tác động tiêu cực tiềm ẩn của việc trung hòa mCRP lên các tế bào mô bình thường, việc điều hòa bổ sung cần được nhắm mục tiêu một cách có chọn lọc vào các tế bào ác tính. Trong nghiên cứu này, các RNA nhỏ can thiệp (siRNA) chống mCRP đã được bao gói trong lipoplex liên hợp transferrin để cung cấp cụ thể đến các tế bào u có CD71 cao BT474, DU145 và SW480 cũng như các tế bào khối u CD71-gõ thấp tương ứng (CD71low). Việc giao hàng có chọn lọc bằng lipoplex transferrin-siRNA trở nên khả thi thông qua việc trung hòa điện tích và đạt được hiệu quả im lặng hóa tất cả ba mCRP lên đến 90%, tùy thuộc vào biểu hiện CD71 của chúng. Việc giảm mCRP dẫn đến sự gia tăng đáng kể của CDC trên các tế bào khối u CD71high với mức tăng 68% ở BT474, 58% ở DU145, và 40% ở SW480 nhưng chỉ tăng nhẹ ở các tế bào CD71low. Việc điều chỉnh giảm CD46 và CD55 đã làm tăng đáng kể quá trình opson hóa C3 chỉ trên các tế bào khối u CD71high. Kết quả của chúng tôi chứng minh lần đầu tiên rằng thông qua việc giao hàng cụ thể siRNA chống mCRP qua thụ thể transferrin, việc điều hòa bổ sung có thể được trung hòa một cách có chọn lọc, cho phép tiêu diệt tế bào khối u do kháng thể trung gian mà không ảnh hưởng đến các tế bào bình thường xung quanh, điều này dường như là một chiến lược phù hợp để cải thiện liệu pháp miễn dịch ung thư dựa trên kháng thể.
Từ khóa
#mCRP #siRNA #transferrin #tua cell #CDC #liệu pháp miễn dịch ung thưTài liệu tham khảo
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