title: Co-Delivery of Epirubicin and siRNA Using Functionalized Mesoporous Silica Nanoparticles Enhances In vitro and In vivo Drug Efficacy.
abstract: Development of drug resistance to anticancer drugs is an important challenge for cancer treatment. Recent studies focus on co-delivery of anticancer drugs and siRNA to overcome this challenge. Mesoporous silica nanoparticles (MSNs) are one of the promising nanoparticles that enable the delivery of drugs and siRNA simultaneously. MSNs coated with copolymer capable of co-delivery of drug and siRNA were prepared and characterized. In the present study, MSNs functionalized with polyethylenimine-polyethylene glycol (PEI-PEG) copolymer were prepared. MSNs were characterized using dynamic light scattering (DLS), Transmission Electron Microscopy (TEM) and elemental analysis. Nanoparticles were loaded with epirubicin hydrochloride (EPI) and anti B-cell lymphoma 2 (BCL-2) siRNA. The in vitro cytotoxicity and in vivo efficacy of different formulations were evaluated. Mean size of MSNs ranged from 98 to 247 nm. EPI release from MSNs was pH-dependent. MSNs loaded with EPI and siRNA showed better in vitro cytotoxicity with 1 μg/mL EPI and 50-400 ng/mL siRNA, besides MSNs loaded with 9 mg/kg EPI and 1.2 mg/kg siRNA resulted in improved in vivo effects compared to EPI or MSNs containing EPI or siRNA alone. The results of in vitro and in vivo studies indicated the synergistic effect of EPI and anti BCL-2 siRNA. This formulation could be a promising nanoparticle for codelivery of drug and siRNA in cancer cells.
authors.forename: Mohammad Yahya
authors.initials: MY
authors.lastname: Hanafi-Bojd
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
authors.forename: Navid
authors.initials: N
authors.lastname: Ramezanian
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
authors.forename: Bizhan
authors.initials: B
authors.lastname: Malaekeh-Nikouei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D015251:Epirubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D016062:Porosity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D015251:Epirubicin; D012822:Silicon Dioxide; D011094:Polyethyleneimine