The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Zhuangqun Yang - One of the best experts on this subject based on the ideXlab platform.
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delivery of sodium morrhuate to hemangioma endothelial cells using Immunoliposomes conjugated with anti vegfr2 kdr antibody
International Journal of Nanomedicine, 2017Co-Authors: Xiaoyong Ren, Jianmin Liang, Zhenghui Wang, Zhuangqun YangAbstract:Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate Immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate Immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate Immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes. Taken together, these results indicate that sodium morrhuate Immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate Immunoliposomes may represent a promising agent in the treatment of hemangiomas.
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Delivery of sodium morrhuate to hemangioma endothelial cells using Immunoliposomes conjugated with anti-VEGFR2/KDR antibody
International journal of nanomedicine, 2017Co-Authors: Xiaoyong Ren, Jianmin Liang, Zhenghui Wang, Zhuangqun YangAbstract:Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate Immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate Immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate Immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes. Taken together, these results indicate that sodium morrhuate Immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate Immunoliposomes may represent a promising agent in the treatment of hemangiomas.
Darrell J Irvine - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle anchoring targets immune agonists to tumors enabling anti cancer immunity without systemic toxicity
Nature Communications, 2018Co-Authors: Yuan Zhang, Na Li, Heikyung Suh, Darrell J IrvineAbstract:Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)−2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, Immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes, cytokine production, and granzyme expression, demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus, surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities.
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Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity
Nature Communications, 2018Co-Authors: Yuan Zhang, Na Li, Darrell J IrvineAbstract:Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)−2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, Immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes, cytokine production, and granzyme expression, demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus, surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities. Immunostimulatory agents used in cancer treatment often elicit serious toxicities, limiting their clinical application. Here, the authors show that the use of liposomes to intravenously deliver surface-anchored IL-2 and anti-CD137 proteins enables anti-cancer immunity and reduces the toxic side effects.
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Enhancing Adoptive Cell Therapy of Cancer through Targeted Delivery of Small-Molecule Immunomodulators to Internalizing or Noninternalizing Receptors
2017Co-Authors: Yiran Zheng, Li Tang, Llian Mabardi, Sudha Kumari, Darrell J IrvineAbstract:Adoptive cell therapy (ACT) has achieved striking efficacy in B-cell leukemias, but less success treating other cancers, in part due to the rapid loss of ACT T-cell effector function in vivo due to immunosuppression in solid tumors. Transforming growth factor-β (TGF-β) signaling is an important mechanism of immune suppression in the tumor microenvironment, but systemic inhibition of TGF-β is toxic. Here we evaluated the potential of targeting a small molecule inhibitor of TGF-β to ACT T-cells using PEGylated Immunoliposomes. Liposomes were prepared that released TGF-β inhibitor over ∼3 days in vitro. We compared the impact of targeting these drug-loaded vesicles to T-cells via an internalizing receptor (CD90) or noninternalizing receptor (CD45). When lymphocytes were preloaded with Immunoliposomes in vitro prior to adoptive therapy, vesicles targeted to both CD45 and CD90 promoted enhanced T-cell expression of granzymes relative to free systemic drug administration, but only targeting to CD45 enhanced accumulation of granzyme-expressing T-cells in tumors, which correlated with the greatest enhancement of T-cell antitumor activity. By contrast, when administered i.v. to target T-cells in vivo, only targeting of a CD90 isoform expressed exclusively by the donor T-cells led to greater tumor regression over equivalent doses of free systemic drug. These results suggest that in vivo, targeting of receptors uniquely expressed by donor T-cells is of paramount importance for maximal efficacy. This Immunoliposome strategy should be broadly applicable to target exogenous or endogenous T-cells and defines parameters to optimize delivery of supporting (or suppressive) drugs to these important immune effectors
Xiaoyong Ren - One of the best experts on this subject based on the ideXlab platform.
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delivery of sodium morrhuate to hemangioma endothelial cells using Immunoliposomes conjugated with anti vegfr2 kdr antibody
International Journal of Nanomedicine, 2017Co-Authors: Xiaoyong Ren, Jianmin Liang, Zhenghui Wang, Zhuangqun YangAbstract:Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate Immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate Immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate Immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes. Taken together, these results indicate that sodium morrhuate Immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate Immunoliposomes may represent a promising agent in the treatment of hemangiomas.
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Delivery of sodium morrhuate to hemangioma endothelial cells using Immunoliposomes conjugated with anti-VEGFR2/KDR antibody
International journal of nanomedicine, 2017Co-Authors: Xiaoyong Ren, Jianmin Liang, Zhenghui Wang, Zhuangqun YangAbstract:Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate Immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate Immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate Immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate Immunoliposomes. Taken together, these results indicate that sodium morrhuate Immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate Immunoliposomes may represent a promising agent in the treatment of hemangiomas.
Richard A. Durst - One of the best experts on this subject based on the ideXlab platform.
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development of an immunomagnetic bead Immunoliposome fluorescence assay for rapid detection of escherichia coli o157 h7 in aqueous samples and comparison of the assay with a standard microbiological method
Applied and Environmental Microbiology, 2005Co-Authors: Thomas R Decory, Richard A. Durst, Scott J Zimmerman, Linda A Garringer, Gary Paluca, Heleen H Decory, Richard A MontagnaAbstract:The objective of this study was to develop and optimize a protocol for the rapid detection of Escherichia coli O157:H7 in aqueous samples by a combined immunomagnetic bead-Immunoliposome (IMB/IL) fluorescence assay. The protocol consisted of the filtration or centrifugation of 30- to 100-ml samples followed by incubation of the filter membranes or pellet with anti-E. coli O157:H7 immunomagnetic beads in growth medium specific for E. coli O157:H7. The resulting E. coli O157:H7-immunomagnetic bead complexes were isolated by magnetic separation, washed, and incubated with sulforhodamine B-containing Immunoliposomes specific for E. coli O157:H7; the final immunomagnetic bead-E. coli O157:H7-Immunoliposome complexes were again isolated by magnetic separation, washed, and lysed with a n-octyl--D-glucopyranoside to release sulforhodamine B. The final protocol took less tha n8ht ocomplete and had a detection limit of less than 1 CFU of E. coli O157:H7 per ml in various aqueous matrices, including apple juice and cider. To validate the protocol at an independent facility, 100-ml samples of groundwater with and without E. coli O157:H7 (15 CFU) were analyzed by a public health laboratory using the optimized protocol and a standard microbiological method. While the IMB/IL fluorescence assay was able to identify E. coli O157:H7-containing samples with 100% accuracy, the standard microbiological method was unable to distinguish E. coli O157:H7-spiked samples from negative controls without further extensive workup. These results demonstrate the feasibility of using immunomagnetic beads in combination with sulforhodamine B-encapsulating Immunoliposomes for the rapid detection of E. coli O157:H7 in aqueous samples.
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Modified Immunoliposome sandwich assay for the detection of Escherichia coli O157:H7 in apple cider.
Journal of Food Protection, 2004Co-Authors: Sungsu Park, Richard A. DurstAbstract:Detection of Escherichia coli O157:H7 in fruit juices such as apple cider is necessary for diagnosis of infection and epidemiological investigations. However, inhibitors in the apple cider, such as endogenous polyphenols and acids, often decrease the sensitivity of PCR assays and immunoassays, thus routinely requiring laborious cell separation steps to increase the sensitivity. In the current study, polyethylene glycol (PEG)-derivatized liposomes encapsulating sulforhodamine B were tagged with anti-E. coli O157:H7 antibodies and used in an Immunoliposome sandwich assay for the detection of E. coli O157:H7 in apple cider. Even without prior separation, this assay can detect E. coli O157:H7 in apple cider samples inoculated with as few as 1 CFU/ml after an 8-h enrichment period. The lower limit of detection in pure cultures without enrichment was 7 x 10(3) CFU/ml (280 CFU/40-microl sample). PEGylated Immunoliposomes are suitable as an analytical reagent for the detection of E. coli O157:H7 in fruit juices containing polyphenols.
Yuan Zhang - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle anchoring targets immune agonists to tumors enabling anti cancer immunity without systemic toxicity
Nature Communications, 2018Co-Authors: Yuan Zhang, Na Li, Heikyung Suh, Darrell J IrvineAbstract:Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)−2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, Immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes, cytokine production, and granzyme expression, demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus, surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities.
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Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity
Nature Communications, 2018Co-Authors: Yuan Zhang, Na Li, Darrell J IrvineAbstract:Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)−2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, Immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes, cytokine production, and granzyme expression, demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus, surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities. Immunostimulatory agents used in cancer treatment often elicit serious toxicities, limiting their clinical application. Here, the authors show that the use of liposomes to intravenously deliver surface-anchored IL-2 and anti-CD137 proteins enables anti-cancer immunity and reduces the toxic side effects.
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Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats
2016Co-Authors: Xue-yuan Chen, Yuan Zhang, Shan-mei Wang, Jie RenAbstract:Objective: Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded Immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model. Methods: DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. Results: The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4uC. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. Conclusions: The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the Immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in th
