title: Dextran-g-PEI nanoparticles as a carrier for co-delivery of adriamycin and plasmid into osteosarcoma cells.
abstract: Combination of chemotherapy and gene therapy of cancer has synergistic effects on overcoming drug resistance. Macromolecular materials such as dextran and PEI have been a potential module for chemotherapeutics and gene delivery. Herein, we hypothesize the combinational strategy of chemotherapy and gene therapy in a single dextran-PEI nanoplatform. The physicochemical properties, cytotoxicity, transfection efficiency were investigated in vitro. Ultra-violet spectrum and (1)H NMR revealed adriamycin and PEI were grafted to dextran chain. Agarose gel electrophoresis demonstrated that the migration of plasmid was completely retarded when the N/P ratio of complex was 4. The sizes of DEX-ADM-PEI/DNA nanoparticles decreased and the zeta potentials enhanced with the increasing N/P ratio. Transmission electron microscope indicated a round morphology of the nanoparticles. DEX-ADM-PEI conjugation has higher cytotoxicity, compared to free adriamycin, in MG-63 and Saos-2 osteosarcoma cells but DEX-PEI maintained over 65% cell viability at the concentration of 8 mg/mL. The transfection efficiency of DEX-ADM-PEI/pEGFP-N1 at N/P ratio of 4:1 both in MG-63 and Saos-2 cell were slightly low than that of PEI 25k. But our nanoplatform efficiently delivered both plasmid pEGFP-N1 and adriamycin into osteosarcoma cells. This study demonstrated that DEX-ADM-PEI efficiently and selectively delivered both plasmid pEGFP-N1 and adriamycin to osteosarcoma cells with low cytotoxicity.
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Hua
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
authors.forename: Tongyi
authors.initials: T
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry* / Q000378:metabolism; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism; D010316:Particle Size; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
chemical_list: D000903:Antibiotics, Antineoplastic; D003911:Dextrans; D004337:Drug Carriers; D004317:Doxorubicin; D011094:Polyethyleneimine