Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China.
Department of Pharmacy, Women's and Children's Hospital Afliated to Qingdao University, Qingdao Women's and Children's Hospital, Qingdao, Shandong, 266000, China.
Int J Biol Sci. 2024 Jan 1;20(1):127-136. doi: 10.7150/ijbs.89890. eCollection 2024.
Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.
Tenascin C（TNC）是细胞外基质中的一种富含糖蛋白，其在动脉粥样硬化中的作用具有促动脉粥样硬化或抗动脉粥样硬化效应，这取决于其位置。TNC，尤其是其 C 结构域/异构体（TNC-C），在动脉粥样硬化斑块活跃区域中强烈过表达，但在大多数正常成年组织中几乎检测不到，这表明 TNC 是动脉粥样硬化靶向药物的有前途的递药载体靶标。许多递药载体通过识别 TNC-C 进行了研究，包括 G11、G11-iRGD、TN11、PL1 和 PL3。通过分别识别 TNC-A1 和 TNC，也研究了 F16 和 FNLM。值得注意的是，iRGD 正在进行临床试验。PL1 不仅识别 TNC-C，还识别纤维连接蛋白（FN）的外结构域-B（EDB），这也是动脉粥样硬化靶向药物的有前途的递药载体，几种缀合物正在进行临床试验。F16 缀合物 F16IL2 正在进行临床试验。因此，G11-iRGD、PL1 和 F16 具有巨大的发展价值。此外，ATN-RNA 和 IMA950 分别作为治疗药物和疫苗，通过靶向 TNC 进行了临床试验。因此，靶向 TNC 可以极大地提高动脉粥样硬化靶向药物的成功率和/或特定药物的开发。本综述讨论了 TNC 在动脉粥样硬化中的作用、动脉粥样硬化靶向递药载体和制剂的开发，为针对 TNC 的药物开发提供了知识。
