Milošević Nenad, Rütter Marie, David Ayelet
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Front Med Technol. 2022 Apr 7;4:846065. doi: 10.3389/fmedt.2022.846065. eCollection 2022.
Endothelial cell adhesion molecules have long been proposed as promising targets in many pathologies. Despite promising preclinical data, several efforts to develop small molecule inhibitors or monoclonal antibodies (mAbs) against cell adhesion molecules (CAMs) ended in clinical-stage failure. In parallel, many well-validated approaches for targeting CAMs with nanomedicine (NM) were reported over the years. A wide range of potential applications has been demonstrated in various preclinical studies, from drug delivery to the tumor vasculature, imaging of the inflamed endothelium, or blocking immune cells infiltration. However, no NM drug candidate emerged further into clinical development. In this review, we will summarize the most advanced examples of CAM-targeted NMs and juxtapose them with known traditional drugs against CAMs, in an attempt to identify important translational hurdles. Most importantly, we will summarize the proposed strategies to enhance endothelial CAM targeting by NMs, in an attempt to offer a catalog of tools for further development.
长期以来，内皮细胞粘附分子一直被认为是许多疾病中有前景的靶点。尽管临床前数据很有前景，但开发针对细胞粘附分子（CAMs）的小分子抑制剂或单克隆抗体（mAbs）的多项努力都在临床阶段失败了。与此同时，多年来有许多经过充分验证的用纳米药物（NM）靶向CAMs的方法被报道。从药物递送至肿瘤血管系统、对炎症内皮进行成像或阻断免疫细胞浸润等方面，各种临床前研究已经证明了其广泛的潜在应用。然而，没有纳米药物候选物进入进一步的临床开发阶段。在本综述中，我们将总结靶向CAMs的纳米药物的最先进实例，并将它们与已知的针对CAMs的传统药物并列比较，试图找出重要的转化障碍。最重要的是，我们将总结所提出的通过纳米药物增强内皮CAM靶向性的策略，试图提供一份用于进一步开发的工具目录。
