TAT 蛋白转导结构域作为一种关节内药物传递技术。
The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology.
机构信息
University of Oulu, Oulu, Finland.
Montana State University System, Bozeman, MT, USA.
出版信息
Cartilage. 2021 Dec;13(2_suppl):1637S-1645S. doi: 10.1177/1947603520959392. Epub 2020 Sep 19.
OBJECTIVE
Intra-articular drug delivery holds great promise for the treatment of joint diseases such as osteoarthritis. The objective of this study was to evaluate the TAT peptide transduction domain (TAT-PTD) as a potential intra-articular drug delivery technology for synovial joints.
DESIGN
Experiments examined the ability of TAT conjugates to associate with primary chondrocytes and alter cellular function both and . Further experiments examined the ability of the TAT-PTD to bind to human osteoarthritic cartilage.
RESULTS
The results show that the TAT-PTD associates with chondrocytes, is capable of delivering siRNA for chondrocyte gene knockdown, and that the recombinant enzyme TAT-Cre is capable of inducing genetic recombination within the knee joint in a reporter mouse model. Last, binding studies show that osteoarthritic cartilage preferentially uptakes the TAT-PTD from solution.
CONCLUSIONS
The results suggest that the TAT-PTD is a promising delivery strategy for intra-articular therapeutics.
目的
关节内药物输送在治疗骨关节炎等关节疾病方面具有广阔的前景。本研究旨在评估 TAT 肽转导结构域（TAT-PTD）作为一种潜在的关节内药物输送技术用于滑液关节。
设计
实验检测了 TAT 缀合物与原代软骨细胞结合并改变细胞功能的能力，以及 TAT-PTD 结合人骨关节炎软骨的能力。
结果
结果表明，TAT-PTD 与软骨细胞结合，能够递送 siRNA 以实现软骨细胞基因沉默，并且重组酶 TAT-Cre 能够在报告小鼠模型的膝关节中诱导基因重组。最后，结合研究表明，骨关节炎软骨从溶液中优先摄取 TAT-PTD。
结论
结果表明，TAT-PTD 是一种有前途的关节内治疗药物输送策略。
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