Dexamethasone enhancement of gene expression after direct hepatic DNA injection.

Malone, Robert E.; Hickman, Mary A.; Lehmann-Bruinsma, Karin; Sih, Tracey R.; Walzem, Rosemary L.; Carlson, Don M.; Powell, Jerry S.

doi:10.1016/s0021-9258(18)43966-x

Cited by 73 publications

(6 citation statements)

References 23 publications

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“…For example, DNA complexed with cationic liposomes may be sequestered in the lamellar bodies and unavailable for gene expression (Menon et al, 1992). Previously, naked DNA has been shown to be delivered and efficiently expressed following direct injection into muscle and tumor cells or liver (Malone et al, 1994;Takehara et al, 1996;Yang and Huang, 1996), as well as into skin (Furth et al, 1995;Hengge et al, 1995;Ciernik et al, 1996), without the need for a DNA carrier. The mechanisms controlling the topical delivery of naked plasmid DNA are poorly understood and need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Topical Gene Delivery to Murine Skin

Kashani‐Sabet

Liggitt

et al. 1999

Journal of Investigative Dermatology

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We topically applied naked plasmid DNA containing the luciferase or chloramphenicol acetyltransferase cDNA directly to mouse skin. Gene expression was detected in skin samples as early as 4 h after DNA application, plateaued from 16 to 72 h post-application, and had decreased significantly by 7 d post-application. Reporter gene activity following topical DNA delivery was comparable with that produced by intradermal injection of DNA. Plasmid DNA at concentrations > or =0.25 microg per microl were required to achieve maximal expression levels. Reporter gene expression following topical administration was largely confined to the superficial layers of the epidermis and to hair follicles. Surprisingly, certain cationic liposomes inhibited the efficiency of cutaneous gene transfer. This technique provides a simple, clinically relevant approach to deliver genes to the skin, with potential application in treating a variety of cutaneous disorders.

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Section: Discussionmentioning

confidence: 99%

Topical Gene Delivery to Murine Skin

Kashani‐Sabet

Liggitt

et al. 1999

Journal of Investigative Dermatology

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“…While these nanocarriers allow the real-time tracking and ultrastructural localization of the siRNA delivery system, combining drug delivery and gene therapy in one particle has the potential to enhance the transfection efficiency or to achieve a synergistic/combined effect of drug and gene therapies. − By co-delivering inflammatory suppressors and plasmid DNA (pDNA) through liposomes, Huang and co-workers developed a non-immunostimulatory gene vector (safeplex), which can inhibit the inflammatory toxicity induced by cationic lipids and CpG motif of pDNA . Using cationic core−shell nanoparticles self-assembled from an amphiphilic copolymer, co-delivery of paclitaxel and pDNA/siRNA was achieved by Yang et al .…”

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confidence: 99%

Host−Guest Interaction Mediated Polymeric Assemblies: Multifunctional Nanoparticles for Drug and Gene Delivery

Zhang¹,

Sun²,

Peter

2010

ACS Nano

147

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Novel core-shell structured nano-assemblies are assembled by a β-cyclodextrin containing positively charged host polymer and a hydrophobic guest polymer. The hydrophobic core of this type of assemblies serves as a nano-container to load and release the hydrophobic drugs, while the positively charged hydrophilic shell is able to condense the plasmid DNA and achieve its transfection/ expression in osteoblast cells. These assemblies may be used as a new generation of multi-functional nano-carriers for simultaneous drug delivery and gene therapy. Keywordshost-guest interactions; polymer assemblies; multifunctional nanoparticles; drug delivery; gene delivery Multi-functionalized nanocarriers are attractive in pharmaceutics, medical imaging, biomedical engineering, and gene therapy. 1 For instance, drug delivery, cell targeting and/or multi-modal imaging can be simultaneously achieved by multifunctional inorganic nanoparticles or nanocrystals, inorganic-organic hybrid nanoparticles and polymeric assemblies. [2][3][4][5][6][7][8][9] Studies based on these versatile pharmaceutical nanocarriers have provided profound insights on the intracellular or in vivo distribution, and valuable information on the spatial and temporal interactions of delivery carriers with cells and tissues as well as their intracellular interactions. In addition, multi-functional nanoparticles have also been employed to implement the simultaneous gene delivery, drug delivery and imaging. 6,[10][11][12][13][14] Using cyanine dye (Cy5.5) labeled magnetic nanoparticles conjugated to a synthetic small interfering RNA (siRNA) duplex, Moore and coworkers were able to achieve the in vivo transfer of siRNA and the simultaneous imaging of its accumulation in tumors by high-resolution magnetic resonance imaging and near-infrared in vivo optical imaging. 15 Proton-sponge coated quantum dots were employed by Nie and Gao et al. for siRNA delivery and intracellular imaging. 16 While these nanocarriers allow the real-time tracking and ultrastructural localization of siRNA delivery system, combining drug delivery and gene therapy in one particle has the potential to *To whom correspondence should be addressed: Prof. Peter X Ma, Department of Biologic and Materials Sciences, Macromolecular Science and Engineering Center, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; mapx@umich.edu. Supporting Information Available. 1 H NMR, FT-IR and fluorescence spectra, and titration curves. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2011 February 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript enhance the transfection efficiency or to achieve a synergistic/combined effect of drug and gene therapies. [17][18][19][20] By co-delivering inflammatory suppressors and plasmid DNA (pDNA) through liposomes, Huang and coworkers developed a non-immunostimulatory gene vector (safeplex), which...

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“…Already in 1994 it was believed that dexamethasone could improve the therapeutic potential of NA due to its antiinflammatory and immune suppressive action [18]. Indeed, dexamethasone pretreatment enhanced luciferase expression in hepatocytes both in vitro and in vivo independent of the applied promoter sequence on the plasmid.…”

Section: Dexamethasone and Other Steroidsmentioning

confidence: 99%

“…For instance, Fraley and colleagues were the first to report enhanced pDNA transfection in vitro upon a chloroquine (CLQ) pretreatment in 1981 [17]. In 1994, Malone et al found subcutaneous dexamethasone injections to improve the transfection of hepatocytes by intrahepatically injected pDNA [18]. Despite an initial wave of promising results, this concept left the foreground of the NA delivery field.…”

Section: Introductionmentioning

confidence: 99%