title: The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes.
abstract: The strong anticancer activity of disulfiram is hindered by its rapid degradation in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation and delivery of disulfiram into breast cancer tumor using passive (EPR effect) and active (folate receptor) targeting. The anticancer activity of disulfiram and its effect on caspase-3 activity and cell cycle are studied. The administration of encapsulated PLGA NPs using intra-peritoneal, intravenous and intra-tumor routes is investigated using animal model. Disulfiram shows strong cytotoxicity against MCF7 cell line. The activity of caspase-3 inhibited with disulfiram via dose dependent manner while the drug causes cell cycle arrest in G0/G1 and S phase time-dependently. The encapsulated disulfiram shows higher activity in apoptosis induction as compared to free drug. In nontoxic dose of encapsulated disulfiram, the highest and lowest efficacy of NPs in tumor growth inhibition is observed for intravenous injection and intraperitoneal injection. It is suggested that administration of disulfiram by targeted PLGA nanoparticles using intravenous injection would present an alternative therapeutic approach for solid tumor treatment.
authors.affiliation: Tissue engineering and biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran 14965/161, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Fasehee
authors.affiliation: Hematology, Oncology and Stem cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Zarrinrad
authors.affiliation: Department of Pathology, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Tavangar
authors.affiliation: Hematology, Oncology and Stem cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran. Electronic address: Shghaffari200@yahoo.com.
authors.forename: Seyed Hamidollah
authors.initials: SH
authors.lastname: Ghaffari
authors.affiliation: Tissue engineering and biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran 14965/161, Iran. Electronic address: sfaghihi@nigeb.ac.ir.
authors.forename: Shahab
authors.initials: S
authors.lastname: Faghihi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004221:Disulfiram / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D036401:Toxicity Tests, Chronic; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D053148:Caspase 3; D004221:Disulfiram
keywords: Administration route; Breast cancer; Disulfiram delivery; MCF7 cells; PLGA nanoparticles