化合物和纳米颗粒向肿瘤的组织穿透递送。
Tissue-penetrating delivery of compounds and nanoparticles into tumors.
作者信息
Sugahara Kazuki N, Teesalu Tambet, Karmali Priya Prakash, Kotamraju Venkata Ramana, Agemy Lilach, Girard Olivier M, Hanahan Douglas, Mattrey Robert F, Ruoslahti Erkki
机构信息
Vascular Mapping Center, Burnham Institute for Medical Research at UCSB, Biology II Building, University of California, Santa Barbara, Santa Barbara, CA 93106-9610, USA.
出版信息
Cancer Cell. 2009 Dec 8;16(6):510-20. doi: 10.1016/j.ccr.2009.10.013.
Poor penetration of drugs into tumors is a major obstacle in tumor treatment. We describe a strategy for peptide-mediated delivery of compounds deep into the tumor parenchyma that uses a tumor-homing peptide, iRGD (CRGDK/RGPD/EC). Intravenously injected compounds coupled to iRGD bound to tumor vessels and spread into the extravascular tumor parenchyma, whereas conventional RGD peptides only delivered the cargo to the blood vessels. iRGD homes to tumors through a three-step process: the RGD motif mediates binding to alphav integrins on tumor endothelium and a proteolytic cleavage then exposes a binding motif for neuropilin-1, which mediates penetration into tissue and cells. Conjugation to iRGD significantly improved the sensitivity of tumor-imaging agents and enhanced the activity of an antitumor drug.
药物在肿瘤中的低渗透性是肿瘤治疗的主要障碍。我们描述了一种通过肽介导将化合物深入递送至肿瘤实质的策略，该策略使用肿瘤归巢肽iRGD（CRGDK/RGPD/EC）。静脉注射与iRGD偶联的化合物会与肿瘤血管结合并扩散到血管外肿瘤实质中，而传统的RGD肽仅将货物递送至血管。iRGD通过三步过程归巢至肿瘤：RGD基序介导与肿瘤内皮细胞上的αv整合素结合，然后蛋白水解切割暴露神经纤毛蛋白-1的结合基序，该基序介导穿透组织和细胞。与iRGD偶联显著提高了肿瘤成像剂的敏感性，并增强了抗肿瘤药物的活性。
Zotero 插件