Chen Tijia, Song Xu, Gong Ting, Fu Yao, Yang Liuqing, Zhang Zhirong, Gong Tao
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Colloids Surf B Biointerfaces. 2017 Aug 1;156:330-339. doi: 10.1016/j.colsurfb.2017.05.038. Epub 2017 May 15.
For glioma as one of the most common and lethal primary brain tumors, the presence of BBB, BBTB, vasculogenic mimicry (VM) channels and tumor-associated macrophages (TAMs) are key biological barriers. Here, a novel drug delivery system which could efficiently deliver drugs to glioma by overcoming multi-barriers and increase antitumor efficacy through multi-therapeutic mechanisms was well developed. In this study, a multi-target peptide nRGD was used to transport across the BBB, mediate tumor penetration and target TAMs. Lycobetaine (LBT) was adopted to kill glioma cells and octreotide (OCT) was co-delivered to inhibit VM channels and prevent angiogenesis. LBT-OCT liposomes (LPs) showed controlled release profile in vitro, increased uptake efficiency, improved inhibitory effect against glioma cells and VM formation, and enhanced BBB-crossing capability. The median survival time of glioma-bearing mice administered with LBT-OCT LPs-nRGD was significantly longer than LBT-OCT LPs (P<0.01). Besides, nRGD achieved a stronger inhibitory effect against tumor associated macrophages (TAMs) compared to LPs-iRGD treatment groups in vivo. Thus, LPs-nRGD represented a promising versatile delivery platform for combination drug therapy in glioma treatment.
作为最常见且致命的原发性脑肿瘤之一，胶质瘤中血脑屏障（BBB）、血脑肿瘤屏障（BBTB）、血管生成拟态（VM）通道和肿瘤相关巨噬细胞（TAM）的存在是关键的生物学屏障。在此，一种新型药物递送系统得以成功开发，该系统能够通过克服多重屏障将药物高效递送至胶质瘤，并通过多种治疗机制提高抗肿瘤疗效。在本研究中，一种多靶点肽nRGD被用于穿越血脑屏障、介导肿瘤渗透并靶向肿瘤相关巨噬细胞。采用番茄碱（LBT）来杀死胶质瘤细胞，并共同递送奥曲肽（OCT）以抑制VM通道并防止血管生成。LBT - OCT脂质体（LPs）在体外呈现出控释特性，提高了摄取效率，增强了对胶质瘤细胞和VM形成的抑制作用，并增强了穿越血脑屏障的能力。给予LBT - OCT LPs - nRGD的荷瘤小鼠的中位生存时间显著长于给予LBT - OCT LPs的小鼠（P<0.01）。此外，在体内，与LPs - iRGD治疗组相比，nRGD对肿瘤相关巨噬细胞（TAM）具有更强的抑制作用。因此，LPs - nRGD代表了一种在胶质瘤治疗中用于联合药物治疗的有前景的通用递送平台。
