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<ul>
<li class='active '><a href="http://openwetware.org/wiki/Biomod/2014/Tianjin"><span>Home</span></a></li>
<li class='has-sub'><a href="http://openwetware.org/wiki/Biomod/2014/wiki-2%27.html"><span>Idea</span></a>
<ul>
<li><a href='http://openwetware.org/wiki/Biomod/2014/wiki-2%27.html#motivation'><span>Background</span></a></li>
<li><a href='http://openwetware.org/wiki/Biomod/2014/wiki-2%27.html#design'><span>Motivation</span></a></li>
</ul>
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<li class='has-sub'><a href="http://openwetware.org/wiki/Biomod/2014/experiment.html"><span>Project</span></a>
<ul>
<li><a href='http://openwetware.org/wiki/Biomod/2012/Tianjin/Result/LogicGate'><span>Strand Replacement Reaction</span></a></li>
<li><a href='http://openwetware.org/wiki/Biomod/2012/Tianjin/Result/YDNA'><span> Synthesis of AU-DNA-CY3</span></a></li>
<li><a href='http://openwetware.org/wiki/Biomod/2012/Tianjin/Result/Origami'><span>DNA Origami</span></a></li>
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<li class='active'><a href="http://openwetware.org/wiki/Biomod/2014/result.html"><span>Protocol</span></a>
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<li class='active '><a href="http://openwetware.org/wiki/Biomod/2014/members.html"><span>Members and Acknowledgement</span></a>
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Background
Advantages of light
A revolution in cancer therapy has taken place by the emerging use of laser light to achieve controlled and confined thermal damage in the tumor tissue. Laser, the acronym for light amplification by the stimulated emission of radiation, is an optical source that emits photons in a coherent and narrow beam. Laser light has the characteristics of monochromaticity, coherence, and collimation. These properties provide a narrow beam of high intensity, which transmits deep down into the target location with minimal power loss and great precision.
In recent years, the near infrared (NIR) laser (in the region of 650-1100 nm) mediated photothermal therapy has attracted increased attentions. NIR laser irradiation can induce hyperthermia damage of cancer cells and tumor organ with deep tissue penetration but minimal skin absorbance. NIR is selected in our project due to its low expenditure, abundant source as well as excellent controllability. Additionally, we choose NIR laser as the photothermal trigger also because its irradiation possesses minimal invasiveness and precise spatial-temporal selectivity since its therapeutic effect happens only at the specific site where both light-absorbent and localized photo-irradiation coexist.
Properties of gold nanoparticles (GNPs)
Nanomedicine is currently an active field because new properties emerge when the size of a matter is reduced from bulk to the nanometer scale. These new properties, including optical, magnetic, electronic, and structural properties, make nano-sized particles (generally 1–100 nm) very promising for a wide range of biomedical applications such as targeted therapy. Plasmonic (noble metal) nanoparticles distinguish themselves from other nanoplatforms by their unique surface plasmon resonance (SPR). A special property of these plasmonic nanoparticles is their heat generation resulting from optical stimulation.
[[Image:http://openwetware.org/wiki/Image:%E5%85%89%E7%85%A7%E5%8A%A8%E7%94%BB.gif] Among plasmonic nanoparticles, gold nanoparticles (GNPs) are most extensively investigated because of their inertness, low cytotoxicity, ready multi-functionalization and long history of medical use. GNPs are also attractive due to their facile synthesis, excellent biocompatibility as well as strongly enhanced and tunable optical properties to convert NIR light into local heat. Gold nanoparticles exhibit NIR activated photothermal activity due to their geometry dependent SPR. This SPR, resulting from photon confinement to a small particle size, enhances all the radiative and nonradiative properties of GNPs. Hence GNPs have immense potential for the selective laser photothermal therapy of cancer due to their ability to efficiently convert surface plasmon resonance-enhanced absorbed light into localized heat and thus offering multiple modalities for biological and medical applications.
DNA Origami
Nucleic acids have been used as building blocks for the bottom-up assembly of intricate suprastructures due to their inherent chemical and biological addressability,structural precision, and efficiency of synthesis. As a novel self-assembly method developed in recent years, DNA origami is one of the greatest progress in the field of DNA nanotechnology and DNA self-assembly. In this method, a long scaffold strand (single-stranded DNA from the M13 phage genome, ~7,429 nucleotides long) was folded with the help of hundreds of short ‘staple’ strands into defined two- and three-dimensional (2D and 3D) shapes. Moreover, the nanostructures by DNA origami are predictable, precise, controllable and efficient. The merits also include relatively low requirements for the experimental conditions and operation skills.
A variety of functional biomolecules andnanoparticles can be assembled onto the DNA origami nanoscaffolds, to obtain complicate nanodevices with special functions which can be used to facilitate imaging, targeted delivery, and controlled release of therapeutic compounds. As described, DNA origami possess the capability of transporting molecular payloads to cells, sensing cell surface inputs for conditional, triggered activation, and reconfiguring its structure for payload delivery. DNA origami structures can also be used as molecular pegboards with a resolution of 4–6 nm, and they been widely used in the assembly of heteroelements such as proteins and nanoparticles. Therefore, DNA origami has shown great potential in nanotechnology.
Motivation
Use light instead of strand displacement reaction to open DNA origami:
Generally strand displacement reaction is used to open DNA origami. In that process two strands with partial or full complementarity hybridize and displace one or more pre-hybridized strands. This mechanism allows for the kinetic control of reaction pathways. However, we need to add the substitutive stand to start the process. If we use DNA origami to transport drugs in vivo, it’s difficult and unsafe to add single-stranded DNA to human body to open DNA origami. So we want to open DNA origami in a physical way.
Why light?
We want to use light to open DNA origami because light control has many advantages.
1. Light is low expenditure and easy to get
2. It is convenient to control the intensity of light
3. Light won’t damage human body
In fact, for treatment, only light will produce sufficient power to penetrate the appropriate site with less energy loss. And, light has already been used into medical treatment field for many years, such as photothermal therapy.
And we use visible or near infrared light for inflammation, edema and preventing tissue damage. Besides, the basic phenomena that is reflection, refraction and absorption occurs when matter is exposed to light. Hemoglobin and water, the major absorbers of visible and near-infrared light (NIR light), respectively, have their lowest absorption coefficient in the NIR region around 650–900 nm. So, we choose the NIR light to reduce the loss in energy.
Our design’s performance objectives: Achieving controlled release of the encapsulated cargo with spatial and temporal control remains a challenge. By taking advantage of Au nanoparticles and different strand-displacement reaction, we hope the realization of a controlled-release formulation might be an important part of our design.
We can design a GNP-DNA origami complex in response to light cues.The controlled release of cargo is achieved by varying light intensity of optical stimulation on Au nanoparticles modified on DNA origami. We prospect that the generated heat by GNPs can break the hydrogen bonds of double-strand DNA. The lock is realised by a special strand-displacement reaction which will not be able to reform its native structure once unzip.
We gain the inspiration on the beautiful honeycomb which is one of the nature's most effective structures , for the reason that the hexagonal honeycomb uses the least amount of bees wax and forms the biggest capacity. And for the other design, what is particularly worth mentioning here is that it looks like the gate of Tianjin University.
calculation
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