Overcoming Multidrug Resistance by On-Demand Intracellular Release of Doxorubicin and Verapamil

Multidrug resistance (MDR) is one of the major obstacles to the successful application of cancer chemotherapy. Herein, we developed light-responsive doxorubicin-and-verapamil-coencapsulated gold liposomes to overcome MDR. Upon ns-pulsed laser irradiation, the highly confined thermal effect increased the permeability of the phospholipid bilayer, triggering the release of doxorubicin and verapamil, leading to high concentrations in cells. Free verapamil efficiently inhibited the membrane multidrug resistance proteins (MRPs), while the high concentration of doxorubicin saturated MRPs, thus overcoming MDR. We showed that nanosecond- (ns-) pulsed laser- (532 nm, 6 ns) induced doxorubicin release from gold liposomes depended on laser fluence and pulse number. More than 58% of the doxorubicin was released with a 10-pulse irradiation (100 mJ/cm2). Furthermore, ns laser pulses also liberated doxorubicin from endocytosed gold liposomes into the cytosol in MDA-MB-231-R cancer cells. The cytotoxicity of doxorubicin coencapsulated with verapamil was significantly enhanced upon laser irradiation. This study suggested that light-triggered on-demand release of chemotherapeutic agents and MRP inhibitors could be used advantageously to overcome multidrug resistance.

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Time-Resolved X-Ray Studies During Pulsed-Laser Irradiation of Ge

MRS Proceedings ◽

10.1557/proc-35-119 ◽

1984 ◽

Vol 35 ◽

Author(s):

J.Z. Tischler ◽

B.C. Larson ◽

D.M. Mills

Keyword(s):

Melting Point ◽

Laser Irradiation ◽

Pulsed Laser ◽

Laser Pulses ◽

High Energy ◽

Measured Temperature ◽

Time Resolved ◽

Synchrotron Source ◽

X Ray ◽

Pulsed Laser Irradiation

ABSTRACTSynchrotron x-ray pulses from the Cornell High Energy Synchrotron Source (CHESS) have been used to carry out nanosecond resolution measurements of the temperature distrubutions in Ge during UV pulsed-laser irradiation. KrF (249 nm) laser pulses of 25 ns FWHM with an energy density of 0.6 J/cm2 were used. The temperatures were determined from x-ray Bragg profile measurements of thermal expansion induced strain on <111> oriented Ge. The data indicate the presence of a liquid-solid interface near the melting point, and large (1500-4500°C/pm) temperature gradients in the solid; these Ge results are analagous to previous ones for Si. The measured temperature distributions are compared with those obtained from heat flow calculations, and the overheating and undercooling of the interface relative to the equilibrium melting point are discussed.

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Slim: a Personal Computer Based Software for Simulation of Laser Interaction with Materials

MRS Proceedings ◽

10.1557/proc-236-533 ◽

1991 ◽

Vol 236 ◽

Cited By ~ 1

Author(s):

Rajiv K. Singh ◽

John Viatella

Keyword(s):

Laser Irradiation ◽

Personal Computer ◽

Rapid Heating ◽

Pulsed Laser ◽

Laser Pulses ◽

Time Dependent ◽

Intense Laser ◽

Laser Interaction ◽

History Of ◽

Short Laser Pulses

AbstractA user-friendly, personal computer (PC) based routine called SLIM [Simulation of Laser Interaction with Materials] has been developed to understand the non-equilibrium effects of high intensity, short laser pulses on different materials. By employing an accurate implicit finite difference scheme with varying spatial and temporal node dimensions, the time-dependent thermal history of laser-irradiated material can be accurately and quickly determined. This program can take into account the temperature dependent optical and thermal properties of the solid, time dependent laser pulse intensity, and formation and propagation of the melt and/or vaporization interfaces induced by intense laser irradiation. The program can also simulate thermal effects on multilayer structures exposed to pulsed laser irradiation It is expected that this simulation routine will be indispensable to all researchers working in the area of pulsed laser processing of materials, including rapid heating, melting, annealing, laser doping, laser deposition of thin films and laser solidification processing.

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Interface Temperatures and Temperature Gradients in Silicon During Pulsed Laser Irradiation

MRS Proceedings ◽

10.1557/proc-100-513 ◽

1988 ◽

Vol 100 ◽

Cited By ~ 4

Author(s):

B. C. Larson ◽

J. Z. Tischler ◽

D. M. Mills

Keyword(s):

Heat Flow ◽

Laser Irradiation ◽

Thermal Strain ◽

Pulsed Laser ◽

Laser Pulses ◽

Temperature Gradients ◽

X Ray Diffraction ◽

X Ray ◽

High Gradients ◽

Pulsed Laser Irradiation

ABSTRACTNanosecond-resolution x-ray diffraction has been used to measure the interface and lattice temperatures of silicon during rapid, pulsed-laser induced melting and regrowth in silicon. Measurements have been carried out on <100> and <111> oriented silicon using the (100) and (111) reflections to measure the thermal strain during 30 ns, 1.1 J/cm2 KrF laser pulses. The results indicate overheating to be low (< 2 K/m/s) for both orientations with undercooling rates of 5.6 K/m/s and 11.4 K/m/s for the <100> and <111> orientations, respectively. Observations of higher than expected temperature gradients below the liquidsolid interface have been discussed in terms of restricted heat flow under high gradients.

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YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death

Journal of Biomedicine and Biotechnology ◽

10.1155/2009/535072 ◽

2009 ◽

Vol 2009 ◽

pp. 1-11

Author(s):

Ji Cao ◽

Lei Zhang ◽

Qing Ye ◽

Xinglu Zhou ◽

Jianshu Lou ◽

...

Keyword(s):

Dna Damage ◽

Multidrug Resistance ◽

Cell Lines ◽

Parental Cell ◽

Mitochondrial Pathway ◽

Chemotherapeutic Agents ◽

Multidrug Resistance Proteins ◽

Glycoprotein P ◽

Resistance Proteins ◽

P Glycoprotein

Overexpression of multidrug resistance proteins P-glycoprotein (P-gp, MDR1) causes resistance of the tumor cells against a variety of chemotherapeutic agents. 3-(1-methyl-1H-indol-3-yl)-1-phenyl-4-(1-(3-(piperidin-1-yl)propyl)-1H-pyrazolo[3,4-b]pyridine-3-yl)-1H-pyrrole-2,5-dione (YQ36) is a novel analogue of bisindolylmaleimide, which has been reported to overcome multidrug resistance. Here, we dedicated to investigate the anticancer activity of YQ36 on KB/VCR cells. The results revealed that YQ36 exhibited great antiproliferative activity on three parental cell lines and MDR1 overexpressed cell lines. Moreover, the hypersensitivity of YQ36 was confirmed on the base of great apoptosis induction and unaltered intracellular drug accumulation in KB/VCR cells. Further results suggested that YQ36 could not be considered as a substrate of P-gp, which contributed to its successfully escaping from the efflux mediated by P-gp. Interestingly, we observed that YQ36 could accumulate in nucleus and induce DNA damage. YQ36 could also induce the activation of caspase-3, imposing effects on the mitochondrial function. Collectively, our data demonstrated that YQ36 exhibited potent activities against MDR cells, inducing DNA damage and triggering subsequent apoptosis via mitochondrial pathway.

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Pulsed Laser Mixing of Metal Overlayers on Ceramics

MRS Proceedings ◽

10.1557/proc-100-653 ◽

1988 ◽

Vol 100 ◽

Cited By ~ 1

Author(s):

R. K. Singh ◽

N. Biunno ◽

J. Narayan

Keyword(s):

Electron Microscopy ◽

Laser Irradiation ◽

Pulsed Laser ◽

Laser Pulses ◽

Intense Laser ◽

Interfacial Layers ◽

Transmission Electron ◽

Modification Technique ◽

Mixed Layers ◽

Metal Overlayers

ABSTRACTPulsed laser mixing has been used as surface modification technique for the improvement in the mechanical properties of ceramics. Thin metallic layers of nickel were deposited on structural silicon nitride and were irradiated with Xenon Chloride (XeCl) laser pulses. The laser parameters were optimized to lead to the formation of mixed layers. The mixed interfacial layers were analyzed using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Rutherford Backscattering (RBS) techniques. Detailed heat flow calculations were performed to simulate the effects of intense laser irradiation on metal coated ceramic structures. The melt lifetimes and the interfacial temperatures obtained using these calculations, were applied to understand the laser mixing phenomena occuring in these layered structures. Thermodynamics of chemical reactions between the metal overlayers and the substrate were done to predict the formation of mixed interfacial layers during laser irradiation.

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Etching-enhanced Ablation and the Formation of a Microstructure in Silicon by Laser Irradiation in an SF6 Atmosphere

Journal of Materials Research ◽

10.1557/jmr.2002.0148 ◽

2002 ◽

Vol 17 (5) ◽

pp. 1002-1013 ◽

Cited By ~ 19

Author(s):

S. Jesse ◽

A. J. Pedraza ◽

J. D. Fowlkes ◽

J. D. Budai

Keyword(s):

Laser Irradiation ◽

Total Pressure ◽

Pulsed Laser ◽

Laser Pulses ◽

Inert Gas ◽

Gas Mixture ◽

Maximum Height ◽

Initial Surface ◽

Charge Coupled Device ◽

Pulsed Laser Irradiation

Sequential pulsed-laser irradiation of silicon in SF6 atmospheres induced the formation of an ensemble of microholes and microcones. Profilometry measurements and direct imaging with an intensifying charge-coupled device camera were used to study the evolution of this microstructure and the laser-generated plume. Both the partial pressure of SF6 and the total pressure of an SF6-inert gas mixture strongly influenced the maximum height that the microcones attained over the initial surface. The cones first grew continuously with the number of pulses, reached a maximum, and then began to recede as the number of laser pulses increased further. The growth of the cones was closely connected with the evolution of the laser-generated plume.

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Oxidation and Nitridation by Pulsed Laser Irradiation of Solids Immersed in Liquids

MRS Proceedings ◽

10.1557/proc-75-297 ◽

1986 ◽

Vol 75 ◽

Author(s):

S. Roorda ◽

A. Polman ◽

S. B. Ogale ◽

F. W. Saris

Keyword(s):

Laser Irradiation ◽

Rutherford Backscattering Spectrometry ◽

Laser Energy ◽

Pulsed Laser ◽

Laser Pulses ◽

Processing Parameters ◽

Initial Surface ◽

X Ray Diffraction ◽

Compound Formation ◽

Pulsed Laser Irradiation

AbstractNitridation and oxidation of titanium is achieved by pulsed laser irradiation of Ti immersed in liquid ammonia or water. Rutherford Backscattering Spectrometry shows that large amounts of nitrogen and oxygen can be incorporated in the metal surface to a depth of several 1000 Å. X-ray diffraction shows evidence of compound formation. Scanning Electron Microscopy reveals that initial surface texture is smoothed, and that stress induced cracks and holes may appear. Irradiation of Fe and Si immersed in various liquids shows that modification depends on which combination of solid and liquid is used. Influence of processing parameters such as laser-energy density and number of laser pulses on compound formation has been investigated. The process is viewed as a reactive solute incorporation in the laser melted surface layer, followed by compound formation.

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