論文

査読有り 国際誌
2019年10月9日

Chlorotoxin modified morusin-PLGA nanoparticles for targeted glioblastoma therapy.

Journal of materials chemistry. B
  • Srishti Agarwal
  • ,
  • M Sheikh Mohamed
  • ,
  • Toru Mizuki
  • ,
  • Toru Maekawa
  • ,
  • D Sakthi Kumar

7
39
開始ページ
5896
終了ページ
5919
記述言語
英語
掲載種別
DOI
10.1039/c9tb01131e

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.

リンク情報
DOI
https://doi.org/10.1039/c9tb01131e
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31423502