title: PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier.
abstract: Superparamagnetic iron oxide nanoparticle (SPION) holds great potential as a gene delivery system due to its unique properties, such as good biocompatibility and non-invasive targeting ability. In this study, we modified SPION with chitosan-graft-PEI (CHI-g-PEI) and PK11195, to fabricate a mitochondria-targeting gene carrier, PK-CP-SPION. PK-CP-SPION manifested prominent physicochemical properties for magnetic guided gene delivery, and it could effectively condense and protect DNA at proper weight ratios. The in vitro cytotoxicity of PK-CP-SPIONs was mild. Under an external magnetic field, the transfection efficiency of PK-CP-SPIONs was comparable to PEI 25 K with shorter transfection time. PK11195 facilitated the specific accumulation of PK-CP-SPIONs in mitochondria, leading to the leakage of cytochrome c, the dissipation of mitochondrial membrane potential and subsequently the activation of mitochondria apoptosis pathway. These results indicated that with further development, PK-CP-SPIONs could serve as a multifunctional nanoplatform for magnetic targeting gene delivery and mitochondria-targeting therapy, leading enhanced therapeutic effect towards tumor cells.
authors.affiliation: a State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , PR China .
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: b Department of Pharmaceutics , China Pharmaceutical University , Nanjing , PR China .
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: c State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macao , China .
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
authors.affiliation: d Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education) , China Pharmaceutical University , Nanjing , PR China .
authors.forename: Fengguo
authors.initials: F
authors.lastname: Xu
authors.affiliation: e Department of Hematology , The Affiliated Zhongda Hospital of Southeast University , Nanjing , PR China , and.
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , PR China .|b Department of Pharmaceutics , China Pharmaceutical University , Nanjing , PR China .
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.affiliation: a State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , PR China .|b Department of Pharmaceutics , China Pharmaceutical University , Nanjing , PR China .|f Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases , China Pharmaceutical University , Nanjing , PR China.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005290:Ferric Compounds / Q000008:administration & dosage / Q000737:chemistry*; D018390:Gene Targeting / Q000379:methods; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D007624:KB Cells; D060526:Magnetic Fields; D008280:Magnetics / Q000379:methods; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection / Q000379:methods
chemical_list: D005290:Ferric Compounds; D007546:Isoquinolines; C551320:chitosan-graft-polyethylenimine; C000499:ferric oxide; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan; C037850:PK 11195
keywords: Gene therapy; magnetofection; mitochondria-targeting; non-viral vector; superparamagnetic iron oxide nanoparticles