Angiogenic and antiangiogenic gene therapy

Małecki, Maciej; Kołsut, Piotr; Proczka, Robert

doi:10.1038/sj.gt.3302621

Cited by 31 publications

(35 citation statements)

References 120 publications

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“…Targeted drug and gene delivery to vascular endothelial cells (ECs) and smooth muscle cells (SMCs) has increasingly become a focus for treating cardiovascular diseases and dysfunctions, such as coronary artery disease, hypercholesterolemia, hypertension, and restenosis, because of the pivotal role of these cells in controlling and maintaining vascular functions [2][3][4]. In addition, targeted drug and gene delivery to the endothelium is being used to treat cancerous tumors by anti-vascular therapy [5] and myocardial and peripheral ischemia by promoting angiogenesis [6]. Many drug and gene delivery systems are being developed to increase targeting to vascular cells, such as drug-eluting stents [7], catheter-based systems [8], viral vectors [9,10], and targeted liposomes [11] and microbubbles [12].…”

Section: Introductionmentioning

confidence: 99%

Ultrasonically targeted delivery into endothelial and smooth muscle cells in ex vivo arteries

Hallow

Mahajan

Prausnitz

2007

Journal of Controlled Release

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This study tested the hypothesis that ultrasound can target intracellular uptake of drugs into vascular endothelial cells (ECs) at low to intermediate energy and into smooth muscle cells (SMCs) at high energy. Ultrasound-enhanced delivery has been shown to enhance and target intracellular drug and gene delivery in the vasculature to treat cardiovascular disease, but quantitative studies of the delivery process are lacking. Viable ex vivo porcine carotid arteries were placed in a solution containing a model drug, TO-PRO ® -1, and Optison ® microbubbles. Arteries were exposed to ultrasound at 1.1 MHz and acoustic energies of 5.0, 66, or 630 J/cm 2 . Using confocal microscopy and fluorescent labeling of cells, the artery endothelium and media were imaged to determine the localization and to quantify intracellular uptake and cell death. At low to intermediate ultrasound energy, ultrasound was shown to target intracellular delivery into viable cells that represented 9 -24% of exposed ECs. These conditions also typically caused 7 -25% EC death. At high energy, intracellular delivery was targeted to SMCs, which was associated with denuding or death of proximal ECs. This work represents the first known in-depth study to evaluate intracellular uptake into cells in tissue. We conclude that significant intracellular uptake of molecules can be targeted into ECs and SMCs by ultrasound-enhanced delivery suggesting possible applications for treatment of cardivascular diseases and dysfunctions.

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Section: Introductionmentioning

confidence: 99%

Ultrasonically targeted delivery into endothelial and smooth muscle cells in ex vivo arteries

Hallow

Mahajan

Prausnitz

2007

Journal of Controlled Release

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“…Because angiogenesis is essential for tumor progression, its inhibition makes a plausible anticancer strategy (4)(5)(6). Several approaches have been used to inhibit tumor angiogenesis and prevent tumor progression, including gene therapy, immunotherapy, or chemotherapy (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Dong¹,

Swettenham²,

Eliasson³

et al. 2007

Cancer Research

104

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“…Gene therapy and gene preparations represent a novel therapeutic approach in contemporary medicine. the focus lies on engineering gene transfer vectors that effectively deliver to cancers genes, thereby encoding therapeutic proteins such as antiangiogenic (soluble receptors of vascular endothelial growth factors), proapoptotic (caspases, tissue inhibitors of matrix metalloproteinases) or immunomodulating (interleukins) (16). Cancer gene therapy is currently one of the most advanced gene therapy strategies found in the clinic (4).…”

Section: Discussionmentioning

confidence: 99%

Recombinant adeno-associated viruses (rAAV2) facilitate the intraperitoneal gene delivery to cancer cells

Małecki

Proczka²,

Chorostowska‐Wynimko³

et al. 2010

Oncology Letters

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Abstract. Peritoneal dissemination of cancer cells is characteristic of advanced stages of ovarian, breast and lung cancers, and is associated with poor patient survival. the presence of cancer cells in effusions complicates treatment protocols, while cell eradication is seriously limited. one of the novel options available is cancer gene therapy with recombinant adeno-associated viruses. this combination represents the most promising gene delivery vehicles to neoplasmatic cells within serosal cavities due to their unique properties that include the ability to infect proliferating cells of broad host range, as well as the potential of long-term expression. recombinant infectious adeno-associated virus serotype 2 particles (rAAV2) were produced in a helper-free system using an AAV-293 packaging cell line, and quantitatively analyzed by real-time Pcr. Balb/c mice intraperitoneally pre-injected with l1 cancer cells were treated with different doses of rAAV2. subsequently, the mice were sacrificed and intraperitoneal effusions were analyzed for rAAV presence and rAAV/β-galactosidase (lacZ) vector efficiency in order to infect cancer cells within the peritoneal cavity. We reported an efficient infection of L1 cancer cells disseminated into the peritoneal cavity by rAAV2. the expression of reporter genes (GFP and LacZ) attributable to the rAAV cell uptake was closely dependent on an applied multiplicity of infection ratio (MoI). the highest infection efficiency was observed at a MOI of 50 and 200. Our study confirmed the ability of adeno-associated viruses to facilitate gene transferability to cancer cells disseminated in the serosal cavity, as well as the potential usefulness of these viruses as a new approach in cancer gene therapy.

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Angiogenic and antiangiogenic gene therapy

Cited by 31 publications

References 120 publications

Ultrasonically targeted delivery into endothelial and smooth muscle cells in ex vivo arteries

Ultrasonically targeted delivery into endothelial and smooth muscle cells in ex vivo arteries

Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Recombinant adeno-associated viruses (rAAV2) facilitate the intraperitoneal gene delivery to cancer cells

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