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Keywords
(9)
Cytochrome C
Fluorescent Probes
Membrane Potential
multidrug resistance
Nude Mice
Particle Size
Polyethylene Glycol
Signaling Pathway
Lung Cancer
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The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells
The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate
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The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells
(
Citations: 1
)
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Xiao-Xing Wang
,
Yang-Bing Li
,
Hong-Juan Yao
,
Rui-Jun Ju
,
Yan Zhang
,
Ruo-Jing Li
,
Yang Yu
,
Liang Zhang
,
Wan-Liang Lu
Intrinsic
multidrug resistance
(MDR) of cancers remains a major obstacle to successful chemotherapy. A dequalinium
polyethylene
glycol-distearoylphosphatidylethanolamine (DQA-PEG2000-DSPE) conjugate was synthesized as a mitochondriotropic molecule, and mitochondrial targeting resveratrol liposomes were developed by modifying DQA-PEG2000-DSPE on the surface of liposomes for overcoming the resistance. Evaluations were performed on the human lung adenocarcinoma A549 cells and resistant A549/cDDP cells, A549 and A549/cDDP tumor spheroids as well as the xenografted resistant A549/cDDP cancers in nude mice. The yield of DQA-PEG2000-DSPE conjugate synthesized was about 87% and the
particle size
of mitochondrial targeting resveratrol liposomes was approximately 70 nm. The mitochondrial targeting liposomes significantly enhanced the cellular uptake, and selectively accumulated into mitochondria when encapsulating coumarin as the fluorescent probe. Furthermore, mitochondrial targeting resveratrol liposomes induced apoptosis of both non-resistant and resistant cancer cells by dissipating mitochondria membrane potential, releasing
cytochrome c
and increasing the activities of caspase 9 and 3. They also exhibited significant antitumor efficacy in two kinds of cancer cells, in tumor spheroids by penetrating deeply into the core, and in xenografted resistant A549/cDDP cancers in nude mice. Mitochondrial targeting resveratrol liposomes co-treating with vinorelbine liposomes significantly enhanced the anticancer efficacy against the resistant A549/cDDP cells. In conclusion, mitochondrial targeting resveratrol liposomes would provide a potential strategy to treat the intrinsic resistant lung cancers by inducing apoptosis via mitochondria signaling pathway.
Journal:
Biomaterials
, vol. 32, no. 24, pp. 5673-5687, 2011
DOI:
10.1016/j.biomaterials.2011.04.029
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Citations
(1)
DIFFERENTIAL MOLECULAR ADAPTATION TO MONOCROTALINE-INDUCED VERSUS PRESSURE-INDUCED RIGHT VENTRICULAR OVERLOAD
Marc R. Moon
,
Abdulhameed Aziz
,
Anson M. Lee
,
Hersh S. Maniar
,
Nneka N. Ufere
,
Evelyn M. Kanter
,
Kathryn A. Yamada
Journal:
Journal of The American College of Cardiology - J AMER COLL CARDIOL
, vol. 57, no. 14, pp. E1457-E1457, 2011