RRC ID 59887
Author Agarwal S, Mohamed MS, Mizuki T, Maekawa T, Sakthi Kumar D.
Title Chlorotoxin modified morusin-PLGA nanoparticles for targeted glioblastoma therapy.
Journal 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.
Volume 7(39)
Pages 5896-5919
Published 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
Times Cited 2
Human and Animal Cells GI-1(RCB0763)