In Vivo comparative study of lipid/DNA complexes with different In Vitro serum stability: Effects on biodistribution and tumor accumulation

Zhang, Ye; Bradshaw‐Pierce, Erica L.; DeLille, Alexandra; Gustafson, Daniel L.; Anchordoquy, Thomas J.

doi:10.1002/jps.21076

Cited by 54 publications

(45 citation statements)

References 63 publications

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“…We applied the lipoplex conditions of Ramesh 7 which utilize a P/N ratio of 2.6, whereas others have used less DNA. 25,48 Our findings are in alignment with the recently reported result of Mignet et al 26 who tested several percentages of DSPE-PEG2000 in lipoplexes and found that large aggregates occur in case of 1.25% and 2.5%, but not 5% PEG-lipid in the formula. Similarly, a size stabilizing effect exist when more than 4-5 moL% of a mono-alkyl-or cholesteryl-anchored PEG-lipid is incorporated into lipoplexes at neutral charge ratio.…”

Section: Effect Of Pegylation In Vitrosupporting

confidence: 92%

“…Hence it may be amenable to utilize a lower N/P ratio, eg, 1/4 as reported, however that cause a decreased transfection in vivo. 48 Opsonization and uptake by phagocytic cells of the reticuloendothelial system (RES) present in blood was therefore expected in case of all four lipoplexes and indeed approximately 20% of the label resides in the spleen, since phagocytic blood cells accumulate later in the spleen as it was reported for liposome particles previously. 20,63 Furthermore, luciferase activity found in the spleen when using A-0 lipoplexes could indicate successful transfection of RES cells accumulating in this organ (Figure 7b).…”

Section: Effect Of Pegylation In Vivomentioning

confidence: 59%

“…The positive charge of lipoplexes led to interaction with albumin and other serum proteins when exposed to serum or injected intravenously. 48,60 Binding of lipoplexes to serum lipoproteins or complement factor C3 showed that it may have strong influence on particle size, DNA integrity, and transfection ability. [60][61][62] When lipoplex size was assessed in the presence of serum proteins it was found that 5% PEG-lipid prevented a large increase in size over several hours that was observed in the case of non-PEGylated lipoplexes.…”

Section: Effect Of Pegylation In Vivomentioning

confidence: 99%

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In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

Gjetting¹,

Arildsen

Christensen

et al. 2010

IJN

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Section: Effect Of Pegylation In Vitrosupporting

confidence: 92%

Section: Effect Of Pegylation In Vivomentioning

confidence: 59%

Section: Effect Of Pegylation In Vivomentioning

confidence: 99%

See 1 more Smart Citation

In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

Gjetting¹,

Arildsen

Christensen

et al. 2010

IJN

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“…18 Studies have demonstrated that lipoplexes with a high cholesterol content show enhanced tumor distribution. 19 Another study reported that lipoplexes containing folate-cholesterol showed a 50-fold increase in transfection compared with those with folate-DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine). 20 In addition, cholesterol has excellent compatibility with the stereocenters in paclitaxel and may interact with those to form stereocomplexes.…”

mentioning

confidence: 99%

Self-assembled micelles of novel amphiphilic copolymer cholesterol-coupled F68 containing cabazitaxel as a drug delivery system

Song¹,

Tian²,

Huang³

et al. 2014

IJN

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Despite being one of the most promising amphiphilic block copolymers, use of Pluronic F68 in drug delivery is limited due to its high critical micelle concentration (CMC). In this study, we developed a novel F68 derivative, cholesterol-coupled F68 (F68-CHMC). This new derivative has a CMC of 10 μg/mL, which is 400-fold lower than that of F68. The drug-loading capacity of F68-CHMC was investigated by encapsulating cabazitaxel, a novel antitumor drug. Drug-loaded micelles were fabricated by a self-assembly method with simple dilution. The optimum particle size of the micelles was 17.5±2.1 nm, with an entrapment efficiency of 98.1% and a drug loading efficiency of 3.16%. In vitro release studies demonstrated that cabazitaxel-loaded F68-CHMC micelles had delayed and sustained-release properties. A cytotoxicity assay of S180 cells showed that blank F68-CHMC was noncytotoxic with a cell viability of nearly 100%, even at a concentration of 1,000 μg/mL. The IC 50 revealed that cabazitaxel-loaded F68-CHMC micelles were more cytotoxic than Tween 80-based cabazitaxel solution and free cabazitaxel. In vivo antitumor activity against S180 cells also indicated better tumor inhibition by the micelles (79.2%) than by Tween 80 solution (56.2%, P <0.05). Based on these results, we conclude that the F68-CHMC copolymer may be a potential nanocarrier to improve the solubility and biological activity of cabazitaxel and other hydrophobic drugs.

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“…Although the biodistribution and tumor accumulation of plasmid/liposome complex were investigated intensively (42,43), the detailed biodistribution of systematic administration of pGenesil-2-shAURKA/liposome complex needs to be further investigated. Moreover, based on research on the relationship between Aurora A and radiation and chemotherapy of cancer cells (18,25,26), the effect of AURKA-shRNA combined with radiation or chemotherapy might be a future direction.…”

Section: Discussionmentioning

confidence: 99%

A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth

Wan

Huang²,

Yang³

et al. 2010

Int J Oncol

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Abstract. Aurora A plays an essential role in centrosome maturation, separation and in the formation of the mitotic bipolar spindle. Overexpression or amplication of Aurora A gene has been detected in many cancer cell lines and various tumor tissues, including breast cancer, suggesting that Aurora A might be drug target for breast cancer treatment. In the current study, short hairpin RNA targeting Aurora A was cloned into pGenesil-2 plasmid vector and then transfected into MDA-MB-435S and ZR-75-30 human breast cancer cells using cationic liposome. Reduced expression of Aurora A was detected by RT-PCR and Western blot. The effect of pGenesil-2-shAURKA plasmid on tumor growth in MDA-MB-435S xenogenic implantation model was studied. pGenesil-2-shAURKA plasmid inhibited tumor growth significantly by systemantic administration. To further study the underlying mechanisms, cell apoptosis and proliferation were investigated by flow cytometric analysis, propidium iodide staining, TUNEL and Ki-67 immunostaining respectively. Increased apoptosis and reduced cell proliferation were detected in vitro and in vivo studies. In summary, our results suggested that specific knockdown of Aurora A expression by vector based shRNA may be a potential therapy for human breast cancer. IntroductionBreast cancer is the most commonly diagnosed cancer in women worldwide. More than 1.15 million women were diagnosed with breast cancer in 2002 (1). Registry data showed that breast cancer incidence has been increasing since 1973, especially in low and middle-income countries.In China, urban registries showed 20-30% increase in the past decade (2). Current breast cancer incidence and mortality rates (~180,510 and 40,940 cases in 2007 in the United States, respectively) (3) highlight the need to explore alternative therapeutic strategies.The process of cell division is instrumental to the development and progression of tumors, and targeting cell division has been proved as a successful antitumor therapy. A number of trials has addressed the benefit of adding a taxane (paclitaxel or docetaxel) to an anthracycline-based adjuvant chemotherapy regimen in breast cancer (4,5), suggesting that the molecules involved in cell cycle and division may be targets for cancer treatment.Aurora A is an oncogenic serine/threonine kinase that plays an essential role in centrosome maturation, separation and in the formation of the mitotic bipolar spindle in various organisms (6-10). It has been reported that its ectopic expression in immortalized NIH/3T3 cells is sufficient to provoke their transformation, defining Aurora A as an oncogene (11). Overexpression or amplication of Aurora A gene has been detected in many cancer cell lines and various tumor tissues, including breast cancer (reviewed in ref. 12). Nadler et al reported that Aurora A expression defines a population of patients with decreased survival, whereas Aurora B expression does not, suggesting that Aurora A might be the preferred drug target in breast cancer (13).RNA interference is a specific way of g...

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In Vivo comparative study of lipid/DNA complexes with different In Vitro serum stability: Effects on biodistribution and tumor accumulation

Cited by 54 publications

References 63 publications

In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

Self-assembled micelles of novel amphiphilic copolymer cholesterol-coupled F68 containing cabazitaxel as a drug delivery system

A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth

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