論文 - 詳細
| RRC ID | 59887 |
|---|---|
| 著者 | Agarwal S, Mohamed MS, Mizuki T, Maekawa T, Sakthi Kumar D. |
| タイトル | Chlorotoxin modified morusin-PLGA nanoparticles for targeted glioblastoma therapy. |
| ジャーナル | J Mater Chem B |
| Abstract |
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. |
| 巻・号 | 7(39) |
| ページ | 5896-5919 |
| 公開日 | 2019-10-9 |
| DOI | 10.1039/c9tb01131e |
| PMID | 31423502 |
| MeSH | Autophagy / drug effects Biological Transport Brain Neoplasms / drug therapy Brain Neoplasms / pathology Cell Line, Tumor Cytoskeleton / drug effects Cytoskeleton / metabolism Drug Carriers / chemistry* Drug Liberation Flavonoids / chemistry* Glioblastoma / drug therapy* Glioblastoma / pathology Humans Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / metabolism Molecular Targeted Therapy* Nanoparticles / chemistry* Polylactic Acid-Polyglycolic Acid Copolymer / chemistry* Reactive Oxygen Species / metabolism Scorpion Venoms / chemistry* Scorpion Venoms / pharmacology |
| IF | 5.047 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | GI-1(RCB0763) |