title: Co-delivery of Doxorubicin Encapsulated PLGA Nanoparticles and Bcl-xL shRNA Using Alkyl-Modified PEI into Breast Cancer Cells.
abstract: In recent years, much effort has been focused on an appropriate combination of chemotherapeutic drugs and nucleic acids to exploit additive or synergistic therapeutic effects and overcome many obstacles such as the reduction of side effects and drug resistance. Short hairpin RNA (shRNA) has designed to allow the production of small interfering RNA (siRNA) within the cells and offer long-lasting silencing of target genes. In this study, alkyl-modified polyethylenimine (PEI 10 kD) was used for co-delivery of doxorubicin (DOX) encapsulated into poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and Bcl-xL shRNA (one class of molecules that block apoptosis of tumor cells) into breast cancer cells. Our results demonstrated that modification of PEI with alkyl chain could enhance the induction of apoptosis in tumor cells by suppression of Bcl-xL gene using Bcl-xL shRNA more than PEI alone. On the other hand, DOX encapsulated into PLGA had more synergistic effect with shRNA in comparison with DOX alone. In conclusion, combination of PLGA-DOX NPs and alkyl-PEI/shRNA complexes may have promising applications in breast cancer therapy.
authors.affiliation: Biotechnology Section, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.|Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Ebrahimian
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Taghavi
authors.affiliation: School of Medicine, Gonabad University of Medical Sciences, Gonabad University, Gonabad, Iran.|Department of Biotechnology, Higher Education Institute of Rab-Rashid, Tabriz, Iran.
authors.forename: Ahad
authors.initials: A
authors.lastname: Mokhtarzadeh
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. hashemim@mums.ac.ir.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hashemi
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D011095:Polyethylenes / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D007097:Imines; D011095:Polyethylenes; D034741:RNA, Small Interfering; D051020:bcl-X Protein; C505405:poly(ethylene imine); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Co-delivery; Doxorubicin; PLGA; ShRNA