Periodic dielectric structures are typically integrated with a planar waveguide to create photonic band-edge modes for feedback in one-dimensional distributed feedback lasers and two-dimensional photonic-crystal lasers^{1, 2, 3, 4}. Although photonic band-edge lasers are widely used in optics and biological applications, drawbacks include low modulation speeds and diffraction-limited mode confinement^5, 6. In contrast, plasmonic nanolasers can support ultrafast dynamics and ultrasmall mode volumes^7, 8, 9. However, because of the large momentum mismatch between their nanolocalized lasing fields and free-space light, they suffer from large radiative losses and lack beam directionality. Here, we report lasing action from band-edge lattice plasmons in arrays of plasmonic nanocavities in a homogeneous dielectric environment. We find that optically pumped, two-dimensional arrays of plasmonic Au or Ag nanoparticles surrounded by an organic gain medium show directional beam emission (divergence angle <1.5° and linewidth <1.3 nm) characteristic of lasing action in the far-field, and behave as arrays of nanoscale light sources in the near-field. Using a semi-quantum electromagnetic approach to simulate the active optical responses, we show that lasing is achieved through stimulated energy transfer from the gain to the band-edge lattice plasmons in the deep subwavelength vicinity of the individual nanoparticles. Using femtosecond-transient absorption spectroscopy, we verified that lattice plasmons in plasmonic nanoparticle arrays could reach a 200-fold enhancement of the spontaneous emission rate of the dye because of their large local density of optical states.

Source: http://www.nature.com

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�&��t�mprove the delivery rate, Anderson says.

“We believe that these particles can be made more efficient. They’re already very efficient, to the point where micrograms of drug per kilogram of animal can work, but these types of studies give us clues as to how to improve performance,” Anderson says.

Molecular traffic jam

The researchers found that once cells absorb the lipid-RNA nanoparticles, they are broken down within about an hour and excreted from the cells.

They also identified a protein called Niemann Pick type C1 (NPC1) as one of the major factors in the nanoparticle-recycling process. Without this protein, the particles could not be excreted from the cells, giving the siRNA more time to reach its targets. “In the absence of the NPC1, there’s a traffic jam, and siRNA gets more time to escape from that traffic jam because there is a backlog,” says Gaurav Sahay, an MIT postdoc and lead author of the Nature Biotechnology paper.

In studies of cells grown in the lab without NPC1, the researchers found that the level of gene silencing achieved with RNA interference was 10 to 15 times greater than that in normal cells.

Lack of NPC1 also causes a rare lysosomal storage disorder that is usually fatal in childhood. The findings suggest that patients with this disorder might benefit greatly from potential RNA interference therapy delivered by this type of nanoparticle, the researchers say. They are now planning to study the effects of knocking out the NPC1 gene on siRNA delivery in animals, with an eye toward testing possible siRNA treatments for the disorder.

The researchers are also looking for other factors involved in nanoparticle recycling that could make good targets for possibly slowing down or blocking the recycling process, which they believe could help make RNA interference drugs much more potent. Possible ways to do that could include giving a drug that interferes with nanoparticle recycling, or creating nanoparticle materials that can more effectively evade the recycling process.

“This paper describes a new and very important way to improve the potency of siRNA delivery systems by inhibiting proteins that recycle imported material back out of the cell,” says Pieter Cullis, a professor of biochemistry and molecular biology at the University of British Columbia who was not part of the research team. “It is possible that this approach will give rise to the order-of-magnitude improvements in potency required for siRNA-based therapeutics to be more generally effective agents to treat disease.”

The research was funded by Alnylam Pharmaceuticals and the National Heart, Lung, and Blood Institute.

Source: http://web.mit.edu

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X1�@��elial-mesenchymal transition — a process that allows cancer cells to lose their adhesion and become mobile, helping them metastasize.

Other authors of the paper are MIT postdoc Sungmin Son; Stanford University postdoc Dario Amodei; MIT grad students Nathan Cermak, Joon Ho Kang and Vivian Hecht; former MIT postdoc Monte Winslow; Tyler Jacks, the David H. Koch Professor of Biology at MIT and director of the Koch Institute; and Parag Mallick, an assistant professor of radiology at Stanford.

The research was funded by the National Cancer Institute, through MIT’s Physical Sciences Oncology Center and Stanford’s Center for Cancer Nanotechnology Excellence and Translation, and Stand Up to Cancer.

Source: http://web.mit.edu