title: Terminal PEGylated DNA-Gold Nanoparticle Conjugates Offering High Resistance to Nuclease Degradation and Efficient Intracellular Delivery of DNA Binding Agents.
abstract: Over the past 10 years, polyvalent DNA-gold nanoparticle (DNA-GNP) conjugate has been demonstrated as an efficient, universal nanocarrier for drug and gene delivery with high uptake by over 50 different types of primary and cancer cell lines. A barrier limiting its in vivo effectiveness is limited resistance to nuclease degradation and nonspecific interaction with blood serum contents. Herein we show that terminal PEGylation of the complementary DNA strand hybridized to a polyvalent DNA-GNP conjugate can eliminate nonspecific adsorption of serum proteins and greatly increases its resistance against DNase I-based degradation. The PEGylated DNA-GNP conjugate still retains a high cell uptake property, making it an attractive intracellular delivery nanocarrier for DNA binding reagents. We show that it can be used for successful intracellular delivery of doxorubicin, a widely used clinical cancer chemotherapeutic drug. Moreover, it can be used for efficient delivery of some cell-membrane-impermeable reagents such as propidium iodide (a DNA intercalating fluorescent dye currently limited to the use of staining dead cells only) and a diruthenium complex (a DNA groove binder), for successful staining of live cells.
authors.affiliation: School of Chemistry and Astbury Structure for Molecular Biology, University of Leeds , Leeds LS2 9JT, U.K.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: School of Chemistry and Astbury Structure for Molecular Biology, University of Leeds , Leeds LS2 9JT, U.K.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Chemical Engineering, Imperial College London , South Kensington Campus, London SW7 2AZ, U.K.
authors.forename: Deborah
authors.initials: D
authors.lastname: Roebuck
authors.affiliation: Department of Chemistry, Tsinghua University , Beijing 100084, P. R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.affiliation: UCL School of Pharmacy, University College London , 29-39 Brunswick Square, London WC1N 1AX, U.K.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Tsinghua University , Beijing 100084, P. R. China.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Chemistry, University of Sheffield , Sheffield S3 7HF, U.K.
authors.forename: Sreejesh
authors.initials: S
authors.lastname: Sreedharan
authors.affiliation: Department of Chemistry, University of Sheffield , Sheffield S3 7HF, U.K.
authors.forename: Caroline
authors.initials: C
authors.lastname: Glover
authors.affiliation: Department of Chemistry, University of Sheffield , Sheffield S3 7HF, U.K.
authors.forename: Jim A
authors.initials: JA
authors.lastname: Thomas
authors.affiliation: Department of Chemistry, Tsinghua University , Beijing 100084, P. R. China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Chemistry and Astbury Structure for Molecular Biology, University of Leeds , Leeds LS2 9JT, U.K.
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Chemical Engineering, Imperial College London , South Kensington Campus, London SW7 2AZ, U.K.
authors.forename: Rongjun
authors.initials: R
authors.lastname: Chen
authors.affiliation: School of Chemistry and Astbury Structure for Molecular Biology, University of Leeds , Leeds LS2 9JT, U.K.
authors.forename: Dejian
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D000067493:Dynamic Light Scattering; D006046:Gold / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry*; D011419:Propidium / Q000737:chemistry* / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D056831:Coordination Complexes; D004337:Drug Carriers; D007364:Intercalating Agents; D011419:Propidium; D011092:Polyethylene Glycols; D006046:Gold; D012428:Ruthenium; D004317:Doxorubicin; D004247:DNA; D003850:Deoxyribonuclease I
keywords: DNA intercalation reagent; DNA−gold nanoparticle conjugate; DNase resistance; PEGylation; drug delivery