Liu Xiangsheng, Jiang Jinhong, Ji Ying, Lu Jianqin, Chan Ryan, Meng Huan
Department of Medicine, Division of NanoMedicine, University of California, Los Angeles, CA, USA.
California NanoSystems Institute, University of California, Los Angeles, CA, USA.
Mol Syst Des Eng. 2017 Oct 1;2(4):370-379. doi: 10.1039/C7ME00050B. Epub 2017 Aug 16.
Many solid tumor types, such as pancreatic cancer, have a generally poor prognosis, in part because the delivery of therapeutic regimen is prohibited by pathological abnormalities that block access to tumor vasculature, leading to poor bioavailability. Recent development of tumor penetrating iRGD peptide that is covalently conjugated on nanocarriers' surface or co-administered with nanocarriers becomes a popular approach for tumor targeting. More importantly, scientists have unlocked an important tumor transcytosis mechanism by which drug carrying nanoparticles directly access solid tumors (without the need of leaky vasculature), thereby allowing systemically injected nanocarriers more abundantly distribute at tumor site with improved efficacy. In this focused review, we summarized the design and implementation strategy for iRGD-mediated tumor targeting. This includes the working principle of such peptide and discussion on patient-specific iRGD effect in vivo, commensurate with the level of key biomarker (i.e. neuropilin-1) expression on tumor vasculature. This highlights the necessity to contemplate the use of a personalized approach when iRGD technology is used in clinic.
许多实体瘤类型,如胰腺癌,总体预后通常较差,部分原因是病理异常阻碍了肿瘤脉管系统的通路,从而导致治疗方案难以实施,生物利用度不佳。近期,一种肿瘤穿透性iRGD肽共价偶联于纳米载体表面或与纳米载体共同给药的技术成为肿瘤靶向治疗的热门方法。更重要的是,科学家们揭示了一种重要的肿瘤转胞吞作用机制,即载药纳米颗粒可直接进入实体瘤(无需血管渗漏),从而使全身注射的纳米载体能更大量地分布于肿瘤部位,提高疗效。在这篇聚焦综述中,我们总结了iRGD介导的肿瘤靶向治疗的设计与实施策略。这包括该肽的作用原理以及对体内患者特异性iRGD效应的讨论,这与肿瘤脉管系统上关键生物标志物(即神经纤毛蛋白-1)的表达水平相关。这凸显了在临床应用iRGD技术时考虑采用个性化方法的必要性。