Abstract：
:DNA formulated into aggregates with polycationic reagents are referred to by a variety of terms including non-viral vectors, synthetic vectors, lipoplexes, polyplexes and more recently nanoparticles. The capacity for delivery of multiple genes, genomic-sized constructs and siRNA delivery, with a diversity of possible formulations, as well as the possibilities of improved efficiency of in vivo gene deliveries, means that nanoparticles, or nanocomplexes to reflect self-assembling systems, will be investigated with increasing vigour in the coming years. This review briefly outlines the applications and challenges for nanoparticle technologies in the field of gene therapy then focuses on the development of a specific kind of formulation, receptor-targeted nanocomplex (RTN), that we have found to be particularly useful in our gene therapy research. An overriding guiding concept that has emerged in the development of synthetic nanodelivery systems is the idea to develop formulations and structures that mimic viruses, whilst retaining the safety elements of synthetic, non-viral systems. RTNs have been optimised and developed for airway epithelial transfection, leading towards gene therapy for cystic fibrosis and for vascular transfection in vein grafts used in bypass surgery. The modular design of the RTN platform further allows for the testing of specific hypotheses relating to the structure and functional role of components in the formation of stable particles and in the transfection pathway, leading to their ultimate disassembly in the nucleus.
journal_name
Cell Biol Toxicoljournal_title
Cell biology and toxicologyauthors
Hart SLdoi
10.1007/s10565-009-9141-ysubject
Has Abstractpub_date
2010-02-01 00:00:00pages
69-81issue
1eissn
0742-2091issn
1573-6822journal_volume
26pub_type
杂志文章,评审abstract：:Recent studies have demonstrated that the insecticide DDT is a tumor promoting agent. Similar to many other tumor promoting agents, DDT has been shown to inhibit gap junctional intercellular communication (GJIC) between cells in culture, and it has been suggested that DDT-induced loss of communication between adjacent...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00249596
更新日期：1990-04-01 00:00:00
abstract：BACKGROUND AND AIMS:Endoplasmic reticulum (ER) stress is a growing concern for drug-induced toxicity which causes several side effects. Ritonavir, a potent HIV protease inhibitor, induces both ER and mitochondrial stress; however, the missing link between ER stress and mitochondrial damage has been unknown. In the pres...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-018-09451-7
更新日期：2019-06-01 00:00:00
abstract：BACKGROUND:Heat shock proteins (HSP) are induced during cellular stress. Their role is to chaperone cellular proteins giving protection from denaturation and ultimately preventing cell death. Monocytes are key cells involved in atherosclerosis and are highly responsive to HSP induction. Therefore, we wished to examine ...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-009-9134-x
更新日期：2010-06-01 00:00:00
abstract：:The mouse skin cocarcinogens fluoranthene, pyrene, and undecane were used with the indirect-acting carcinogen, benzo(a)pyrene (BP), and the direct-acting alkylating carcinogen, beta-propiolactone (BPL), in an in vitro transformation assay. Dose response, cytotoxicity, and transformation studies with these compounds we...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00118197
更新日期：1985-10-01 00:00:00
abstract：:In previous studies cadmium chloride (CdCl2) nonlethally inhibited Y-1 adrenal mouse adrenal tumour cell 20-dihydroxyprogesterone (20DHP) secretion, affecting unstimulated and stimulated steroidogenic pathway sites differently. We studied CdCl2 effects on unstimulated steroidogenesis using Y-1 cells incubated 0.5 h in...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00757184
更新日期：1994-02-01 00:00:00
abstract：:Although methylguanine-DNA-methyltransferase (MGMT) plays an important role in resistance to temozolomide (TMZ) in glioma, 40% of gliomas with MGMT inactivation are still resistant to TMZ. The underlying mechanism is not clear. Here, we report that forkhead box M1 (FoxM1) transcriptionally activates the expression of ...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-017-9381-1
更新日期：2017-12-01 00:00:00
abstract：:During the last few years the increased presence of proinflammatory cytokines and oxidation products in Alzheimer's disease (AD) has been largely described. Oxysterols, formed by hydroxylation of cholesterol, occur naturally in the brain and are increased in the serum of AD patients. Of these oxysterols, 25-hydroxycho...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1011996515328
更新日期：2001-01-01 00:00:00
abstract：:Cyclosporin A induces in vivo a severe nephrotoxicity characterized by a large decrease in renal hemodynamics. The aim of this study is to establish the ability of the known NO donor 3-morpholinosydnonimine (SIN-1) to prevent the cyclosporin A-induced contraction by using rat isolated glomeruli and cultured glomerular...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00438167
更新日期：1996-12-01 00:00:00
abstract：:Glioblastoma (GBM) is the most aggressive type of glioma. Temozolomide (TMZ) is currently the drug of choice used for post-operative chemotherapy of GBM. However, the presence of intrinsic and acquired resistance hinders the success of chemotherapy. To understand the TMZ resistant mechanisms in glioma, we investigated...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-019-09502-7
更新日期：2020-06-01 00:00:00
abstract：:Uranium is a natural radioactive metallic element; its effect on the organism is cumulative, and chronic exposure to this element can induce carcinogenesis. Three cities of the Amazon region-Monte Alegre, Prainha, and Alenquer-in North Brazil, are located in one of the largest uranium mineralization areas of the world...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-010-9152-8
更新日期：2010-10-01 00:00:00
abstract：:Recent findings suggest a functional interaction of the drug resistance enzyme glutathione S-transferase P (GSTP) with the transcription factor Nrf2, a master regulator of the adaptive stress response to cellular electrophiles. The effect of this interaction on the metabolism and redox of cellular thiols was investiga...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-020-09517-5
更新日期：2020-08-01 00:00:00
abstract：:Ethanol consumption has long been associated with brain damage. However, the mechanism underlying this deleterious effect remains unclear. Among different hypotheses, acetaldehyde is regarded by certain authors as playing a major role in the expression of ethanol toxicity, but there are still some uncertainties about ...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-004-0087-9
更新日期：2004-11-01 00:00:00
abstract：:Cationic lipids are widely used for gene transfer in vitro and show promise as vectors for in vivo gene therapy applications. However, there is limited understanding of the cellular mechanisms involved in nonviral gene transfer. We investigated two major steps that could be limiting barriers to cationic lipid-mediated...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1007425803756
更新日期：1998-03-01 00:00:00
abstract：:Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that endocrine disruptors may also contribute to the pathology of cardiovascular disease. PCB153 is one of the most commonly found polychlorinated biphenyls, and based on epidemiological s...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-010-9170-6
更新日期：2011-02-01 00:00:00
abstract：:New developments in mutagenic risk assessment have appeared in the past few years. New methods have been developed such as in vitro micronucleus assay for chromosomal alterations, comet assay for primary DNA damage, use of transgenic animals to detect in vivo gene mutations, and fluorescent in situ hybridization metho...
journal_title：Cell biology and toxicology
pub_type： 杂志文章,评审
doi：10.1023/a:1007697715084
更新日期：1999-01-01 00:00:00
abstract：:Many of the differentiated functions of hepatocytes are lost in culture, yet addition of certain medium supplements can aid in the retention of differentiated character. Therefore, the effect of time in monolayer culture on rat hepatocyte glutathione (GSH) synthesis and sensitivity to the GSH detoxicated xenobiotic et...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00117851
更新日期：1986-12-01 00:00:00
abstract：:Folic acid (FA) is a vitamin essential for normal cellular functions, growth, and development. Because humans cannot synthesize this micronutrient, it must be obtained from dietary sources through intestinal absorption. The intestinal tract is a major target for oxidative stress. Our aim was to investigate the effect ...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-012-9228-8
更新日期：2012-12-01 00:00:00
abstract：:Although estrogens have been detected in some echinoderm species, their role is not clearly understood; so we examined the effects of estrogens administered to sea urchin embryos and larvae. A typical malformation was exogastrulation, induced by the exposure to ethynylestradiol (EER) in a defined period of 12 h from 1...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-008-9073-y
更新日期：2008-12-01 00:00:00
abstract：:Rats chronically exposed to acrylonitrile (ACN) have shown a dose-dependent increase in the incidence of astrocytomas in the brain. The mechanism(s) by which ACN induces cancer in rodents has not been established. ACN does not appear to be directly genotoxic in the brain and thus a nongenotoxic mode of action has been...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1007685504941
更新日期：1999-06-01 00:00:00
abstract：:Skin intoxication by bis(beta-chloroethyl)sulfide (BCES; sulfur mustard) induces cutaneous lesions similar to thermal burns, characterized by slowness of skin healing. We have developed an in vitro model of skin equivalent to investigate mechanisms involved in this delay. Direct intoxication of dermal equivalent produ...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1007491703271
更新日期：1998-02-01 00:00:00
abstract：:Magnesium, an essential metal that is important in the normal functioning of DNA, has been shown to interact with some of the toxic heavy metals in respect to biochemical and molecular mechanisms and in altering the tumorigenic process. This study examined the influence of magnesium in combination with nickel and cadm...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00756493
更新日期：1994-04-01 00:00:00
abstract：:Cerebral infarction causes severe morbidity and mortality. Most patients with cerebral infarction should take antiplatelet drugs daily, so the effects of those drugs on the regeneration of the brain need to be investigated. Aspirin and clopidogrel are the most widely used antiplatelet drugs for the prevention of ische...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-017-9412-y
更新日期：2018-06-01 00:00:00
abstract：:An in vitro human nasal model was developed as a tool to study the local tolerability of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using Sandostatin (SMS) an octapeptide analog of somatostatin, as a reference drug enhanced by Avicel (microcrystalline...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00757627
更新日期：1995-10-01 00:00:00
abstract：:Although the interactions of sulfur mustard (HD) with nucleic acids and proteins have been well studied, the toxic interactions with the membrane matrix and specially the phospholipid bilayer have so far been poorly investigated. We have used several NMR techniques to study these interactions: 1H NMR to observe the lo...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1020815723009
更新日期：2002-01-01 00:00:00
abstract：:Ten compounds representative of diverse classes of chemicals were evaluated for their cytotoxicity and transforming ability to human skin fibroblasts in vitro. Only five of the ten compounds were highly cytotoxic in the 0-100 micrograms/ml range and their order of cytotoxicity was: 2,5-bis(1-aziridinyl)-3,6-bis(carboe...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00249592
更新日期：1990-04-01 00:00:00
abstract：:RANTES is a chemokine with eosinophil attractant and activating activities. This study was undertaken to determine whether primary cultures of human nasal and primate bronchial epithelial cells produce RANTES and the effect of various cytokines and dexamethasone on the release of this chemokine. Nasal epithelial cells...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1007318514715
更新日期：1997-03-01 00:00:00
abstract：:Quinones are widely distributed in the environment, both as natural products and as pollutants. This paper reports that one of the simplest quinones, 2-methyl-1,4-naphthoquinone (menadione), effectively inhibited apoptosis in the presence of UVA. Menadione suppressed the apoptosis induced by serum depletion and cell d...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-006-0089-x
更新日期：2006-09-01 00:00:00
abstract：:Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation f...
journal_title：Cell biology and toxicology
pub_type： 杂志文章,评审
doi：10.1007/s10565-016-9377-2
更新日期：2017-06-01 00:00:00
abstract：:The polyether toxin, okadaic acid, causes diarrhetic shellfish poisoning in humans. Despite extensive research into its cellular targets using rodent models, we know little about its putative effect(s) on innate immunity. We inoculated larvae of the greater wax moth, Galleria mellonella, with physiologically relevant ...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-018-09448-2
更新日期：2019-06-01 00:00:00
abstract：:Because of a possible role of astrocytes in trialkyltin-induced neurotoxicity in vivo various studies have been performed using cultures of astrocytes or glioma cells in vitro. With respect to cytotoxic potencies of trialkyltins these studies gave rather divergent results. Therefore the aim of the present study was to...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-004-3859-3
更新日期：2004-09-01 00:00:00
