胶质瘤
纳米载体
细胞毒性
癌症研究
PLGA公司
细胞凋亡
U87型
癌细胞
化学
血脑屏障
体外
药物输送
癌症
生物
医学
生物化学
内科学
中枢神经系统
有机化学
作者
Srishti Agarwal,M. Sheikh Mohamed,Toru Mizuki,Toru Maekawa,D. Sakthi Kumar
摘要
Malignant brain tumors remain a major cause of concern and mortality as successful treatment is hindered due to the poor transport and low penetration of chemotherapeutics across the blood-brain barrier (BBB). In this study, a nano formulation composed of chlorotoxin (CTX)-conjugated morusin loaded PLGA nanoparticles (PLGA-MOR-CTX) was devised against Glioblastoma Multiforme (GBM) and its anti-proliferative effects were evaluated in vitro. The synthesized nanoparticles were loaded with morusin, a naturally derived chemotherapeutic drug, and surface conjugated with CTX, a peptide derived from scorpion venom, highly specific for chloride channels (CIC-3) expressed in glioma tumor cells, as well as for matrix metalloproteinase (MMP-2), which is up regulated in the tumor microenvironment. Subsequently, the anti-cancer potential of the NPs was assessed in U87 and GI-1 (human glioblastoma) cells. Antiproliferative, cell apoptosis, and other cell-based assays demonstrated that the PLGA-MOR-CTX NPs resulted in enhanced inhibitory effects on U87 and GI-1 glioma cells. Prominent cytotoxicity parameters such as ROS generation, enhanced caspase activity, cytoskeletal destabilization, and inhibition of MMP-activity were observed in glioblastoma cells upon PLGA-MOR-CTX NP treatment. The cytocompatibility observed with normal human neuronal cells (HCN-1A) and the enhanced lethal effects in glioblastoma cells highlight the potential of PLGA-MOR-CTX nanoparticles as promising therapeutic nanocarriers towards GBM.
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