肿瘤细胞治疗研究
英文原题：Amphiphilic Polyaspartamide Derivatives with Cholesterol Introduction Enhanced Ex Vivo mRNA Transfection Efficiency to Natural Killer Cells.
工程化自然杀伤（NK）细胞通过过表达嵌合抗原受体来消除癌细胞，从而产生高效且安全的NK细胞疗法。
工程化自然杀伤（NK）细胞通过过表达嵌合抗原受体来消除癌细胞，从而产生高效且安全的NK细胞疗法。本研究探讨了融合蛋白GreenLantern-自然杀伤组2D（NKG2D）mRNA的聚复合物制剂，以评估其体外递送至NK细胞的效率，其中NK细胞表面的NKG2D识别癌细胞上对应的NKG2D配体。通过在主链上添加环己基乙胺（CHE）和二亚乙基三胺（DET），并在α端添加胆固醇（Chol），制备了两亲性聚天冬酰胺衍生物Chol-PAsp(DET/CHE)，以增强内体逃逸能力并优化疏水性。Chol-PAsp(DET/CHE)显著提高了mRNA向NK-92mi细胞的递送效率，这归因于聚复合物稳定性的增加和mRNA细胞摄取能力的改善。过表达NKG2D的NK-92mi细胞对人结肠癌细胞表现出高抗癌效力，且不影响成纤维细胞的活力。因此，Chol-PAsp(DET/CHE)可能是一种有前景的mRNA递送载体，用于NK细胞的体外工程化。
Engineered natural killer (NK) cells eliminate cancer cells by overexpressing a chimeric antigen receptor, producing highly efficient and safe NK cell therapies. This study investigated the polyplex formulation for the fusion protein GreenLantern-natural killer group 2D (NKG2D) mRNA to evaluate its ex vivo delivery efficacy into NK cells, wherein NKG2D on the surface of NK cells recognized its counterpart NKG2D ligands on cancer cells. Amphiphilic polyaspartamide derivatives Chol-PAsp(DET/CHE) were prepared by adding cyclohexylethylamine (CHE) and diethylenetriamine (DET) in the side chains and cholesterol (Chol) at the α-terminus to enhance endosomal escapability and optimize hydrophobicity. Chol-PAsp(DET/CHE) significantly improved mRNA delivery efficacy into NK-92mi cells, explained by increased polyplex stability and improved cellular uptake of mRNA. The NKG2D-overexpressing NK-92mi cells exhibited high anticancer efficacy against human colon cancer cells without affecting the viability of fibroblasts. Therefore, Chol-PAsp(DET/CHE) could be a promising mRNA delivery carrier for the ex vivo engineering of NK cells.
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