The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology
The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology
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DOI：
10.1177/1947603520959392
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发表时间：
2020-09-19
期刊：
影响因子：
2.8
通讯作者：
June, Ronald K.
中科院分区：
文献类型：
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作者：
Mailhiot, Sarah E.;Thompson, Matthew A.;June, Ronald K.
目的关节内给药在骨关节炎等关节疾病的治疗中具有广阔的应用前景。本研究的目的是评价TAT多肽转导结构域(TAT-PTD)作为一种潜在的滑膜关节内给药技术。设计实验检测了TAT结合物在体内外与原代软骨细胞结合和改变细胞功能的能力。进一步的实验测试了TAT-PTD与人骨关节炎软骨结合的能力。结果TAT-PTD能与软骨细胞结合，能携带软骨细胞基因敲除的siRNA，重组酶TAT-Cre能在小鼠膝关节内诱导成活重组。最后，结合研究表明，骨关节炎软骨优先从溶液中摄取TAT-PTD。结论TAT-PTD是关节内治疗的一种有前景的给药策略。
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 bothin vitroandin vivo. 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 inducingin vivogenetic 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.