Bhowmik Arijit, Chakravarti Sayak, Ghosh Aparajita, Shaw Rajni, Bhandary Suman, Bhattacharyya Satyaranjan, Sen Parimal C, Ghosh Mrinal K
Signal Transduction in Cancer and Stem Cells Laboratory, Translational Research Unit of Excellence (TRUE), Division of Cancer Biology and Inflammatory Disorder, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata 700091, India.
Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata 700054, India.
Oncotarget. 2017 Jun 27;8(39):65339-65358. doi: 10.18632/oncotarget.18689. eCollection 2017 Sep 12.
Current therapy for Glioblastoma is insufficient because of the presence of blood brain barrier. It limits the transport of essential drugs to the tumor sites. To overcome this limitation we strategized the delivery of an anticancer compound 3,3'-diindolylmethane by encapsulation in poly (lactic-co-glycolic acid) nanoparticles. These nanoparticles were tagged with a novel peptide against somatostatin receptor 2 (SSTR2), a potential target in glioma. The nanoformulation (27-87nm) had loading and encapsulation efficiency of 7.2% and 70% respectively. It was successfully internalized inside the glioma cells resulting in apoptosis. Furthermore, an bio-distribution study revealed the selective accumulation of the nanoformulation into rat brain tumor sites by crossing the blood brain barrier. This resulted in abrogation of epidermal growth factor receptor pathway activation in glioma cells. Our novel nanopreparation therefore shows great promise to serve as a template for targeted delivery of other therapeutics in treating GBM.
由于血脑屏障的存在,目前胶质母细胞瘤的治疗并不充分。血脑屏障限制了必需药物向肿瘤部位的转运。为克服这一限制,我们制定了将抗癌化合物3,3'-二吲哚甲烷封装在聚(乳酸-乙醇酸)纳米颗粒中的策略。这些纳米颗粒用一种针对生长抑素受体2(SSTR2)的新型肽进行标记,SSTR2是胶质瘤中的一个潜在靶点。该纳米制剂(27 - 87纳米)的载药量和包封率分别为7.2%和70%。它成功内化进入胶质瘤细胞导致细胞凋亡。此外,一项生物分布研究表明该纳米制剂能够穿过血脑屏障,选择性地在大鼠脑肿瘤部位蓄积。这导致胶质瘤细胞中表皮生长因子受体途径的激活被消除。因此,我们的新型纳米制剂很有希望作为其他治疗药物靶向递送的模板用于治疗胶质母细胞瘤。