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      <li class='active '><a href="http://openwetware.org/wiki/Biomod/2014/Tianjin"><span>Home</span></a></li>
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              <li><a href='http://openwetware.org/wiki/Biomod/2014/wiki-2%27.html#background'><span>Background</span></a></li>
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                    <li><a href='http://openwetware.org/wiki/Biomod/2014/wiki-2%27.html#motivation'><span>Motivation</span></a></li>
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              <li><a href="http://openwetware.org/wiki/Biomod/2014/experiment.html#Three-arm locker"><span>Three-arm Locker</span></a></li>
                    <li><a href="http://openwetware.org/wiki/Biomod/2014/experiment.html#Gold nanoparticle based photosensor"><span> Gold Nanoparticle Based Photosensor</span></a></li>
                    <li><a href="http://openwetware.org/wiki/Biomod/2014/experiment.html#dna origami"><span>DNA Origami</span></a></li>
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            <li class='active'><a href="http://openwetware.org/wiki/Tianjin_protocol"><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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<a name="background"></html>
      <td align="center"><p><strong>DESIGN</strong></p></td>
==Background==
    </tr>
<html></a></html>
    <tr>
<big>DNA Origami</big>
      <td align="center"><p><strong>ABSTRACT</strong></p></td>
 
    </tr>
The unique structural motifs and molecular recognition properties of DNA make it a promising template for building nanostructures. Using a long single-stranded DNA as a template, a novel strategy, the so-called DNA origami method, has been developed for the preparation of various two-dimensional (2D) and three-dimensional (3D) nanostructures with defined size which is predictable, precise, controllable and efficient.<br><br>  
    <tr>
 
      <td align="center"><p><strong>GOAL</strong></p></td>
[[Image:fig02.gif|thumb|550px|center|Fig 1.DNA origami and its applications.<br>]]
    </tr>
 
    <tr>
DNA origami is an excellent plantform for the nanopatterning and a variety of functional biomolecules and nanoparticles 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 hetero-elements such as proteins and nanoparticles. Therefore, DNA origami has shown great potential in nanotechnology.<br>
      <td>&nbsp;</td>
 
    </tr>
<big>Advantages of light</big>
  </table>
 
</div>
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. <br>
<div id="cd2" onMouseOver="MM_showHideLayers('cd2','','show')" onMouseOut="MM_showHideLayers('cd2','','hide')">
 
  <table width="100%" border="2" cellpadding="2" cellspacing="2" class="bq1">
<big>Properties of gold nanoparticles (GNPs)</big>
    <tr>
 
      <td align="center"><p>MATERIALS</p></td>
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. <br><br>
    </tr>
 
    <tr>
[[Image:fig01.gif|thumb|550px|center|Fig 2.The photothermal property for gold nanoparticle.<br>]]
      <td align="center"><p>METHODS</p></td>
 
    </tr>
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 light into local heat. Gold nanoparticles exhibit light 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. <br>
    <tr>
[[Image:那张图.jpg|thumb|550px|center|Fig 3.The the therapy use of gold nanoparticle and DNA origami.<br>]]
      <td align="center"><p>DISCUSSION</p></td>
 
    </tr>
 
    <tr>
<html><a name="motivation"></html>
      <td align="center"><p>&nbsp;</p></td>
==Motivation==
    </tr>
<html></a></html>
  </table>
 
</div>
DNA origami is also emerging as a strong candidate for drug delivery in living systems. For its high compatibility to so many kinds of molecules, such as functional biomolecules and nanoparticles which can be linked to the DNA origami scaffolds, to obtain complicated functional nano-devices. Besides, it's capability to fold structures of 2-dimentional or 3-dimentional makes it will get more circumstances to apply. What’s more, the high rate of development and the endless potential of DNA origami make it worth researching.
<div id="apDiv1">
 
  <table width="234" border="2" cellspacing="2">
But the methods of opening an origami box or changing the structure of it is limited in the addition of ssDNA to open by strand replacement or chemical methods to break, which limits the  applications of  origami especially in vivo. So, a physical way without adding anything to achieve the goal is what we need and search for. We choose light. But why?
    <tr>
 
      <th class="bq2" scope="row">PROJECT</th>
We want to use light to open DNA origami because light control has many advantages.
    </tr>
  </table>
1. Light is low expenditure and easy to get.
  <table width="200" border="2" cellpadding="2" cellspacing="2" class="bq1">
 
    <tr>
2. It is convenient to control the intensity of light.
      <td align="left"><a href="#motivation">※MOTIVATION</a></td>
 
    </tr>
3. Light for therapeutic could cause less damage on tissue.
    <tr>
 
      <td align="left"><a href="#design">※DESIGN</a><a href="#abstract"></a></td>
In fact, in treatment, only light will produce sufficient power to penetrate the specific site with less energy loss. And, light has already been used into medical treatment field for many years, such as photothermal therapy. Then, the next question is how to change the light into heat, and the traditional way of photothermal therapy may answer this question.
    </tr>
 
    <tr>
A type of nanomaterial with strong light absorption comes into the sight of us, which is named gold nanoparticle (Au NP). Au NP has immense potential for the selective laser photothermal therapy of cancer cells due to its photo-thermal activity. It can convert light into heat, and leads to a temperature increase, which serves as our opening trigger.
      <td align="left"><a href="#process">※PROCESS</a></td>
 
    </tr>
And as all we know, origami is locked by complementary DNA sequence, which is difficult to totally separate by heating and restoring to room temperature. So that means our origami box have a large possibility to reclose after its open. To overcome this problem, we design three-arm DNA lock to “intelligently” control the open and close of origami by displacement, and it will be showed in the next part.
    <tr>
 
      <td>&nbsp;</td>
All in all, by creating and utilizing these principle or design, we want to grant this device with the following control characteristics:
    </tr>
Local release of drugs. Traditional drugs are transported to every corner in human body, and may attack all the cells including the normal ones,such as the low specificity of anticancer drugs. However, our device is supposed to release at a specific location in human body under control.
    <tr>
 
      <td><img src="1.png" alt="" width="219" height="300" /></td>
 
    </tr>
<big>Selective release of drugs</big>
  </table>
 
  <p>&nbsp;</p>
We want to give our device a DNA logical gate, which enable the device to selectively release specific drugs aimed at curing different cells under different conditions.
</div>
 
<div class="bq1" id="apDiv2"><a name="process" id="process"></a><span class="bq3">※PROCESS</span></div>
<big>Physical control</big>
<div id="apDiv8"><a href="#" onMouseOut="MM_swapImgRestore()" onMouseOver="MM_swapImage('Image4','','20090115201834758.jpg',1)"><img src="1.gif" name="Image4" width="129" height="129" border="0"></a></div>
 
<div class="bq1" id="apDiv9"><img src="Tianjin_index15.png" width="45" height="45" align="absmiddle"><a name="motivation" id="motivation"></a><span class="bq3">※MOTIVATION</span></div>
We replace traditional control methods of adding chemicals with a physical trigger to make our device tunable for future modification, which has never done before.
<div class="js" id="apDiv10"> <strong>A. Use  light instead of strand displacement to open DNA origami.
 
  </strong>
 
  <p>&nbsp;&nbsp;&nbsp; <span class="bq1">Generally  strand displacement is used to open DNA origami. If we use DNA origami to  transport drugs in human body, it&rsquo;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.<br>
<html><a name="calculation"></html>
  &nbsp;&nbsp;&nbsp; We  want to use light to open DNA origami because light control has many  advantages.</span></p>
 
  <ol>
==Calculation==
    <li class="bq1">light is cheap and easy to get</li>
<html></a></html>
    <li class="bq1">it is convenient to control the intensity of light</li>
<big>Equation of △T</big>
    <li class="bq1">light  won&rsquo;t damage human body
 
      <hr>
WHEN
    </li>
 
  </ol>
1、the NPs are far enough（ interdistance is at least 4 or 5 times larger than the NP diameter ）
  <p class="js"><strong>B. Open  different DNA origami selectively</strong></p>
 
  <p class="bq1">&nbsp;&nbsp;&nbsp; In  severe and advanced tumors, combined drug chemotherapy is gaining importance,  which has already been proven to be clinically successful. Cancer stem cells  that are diagnosed pose a new challenge to existing chemotherapy and radiation  therapies, as they are intrinsically resistant by being inactive or adopting a drug efflux mechanism or enhanced antiapoptotic protein and DNA repairing  ability. Hence to cure this, drug combinations are explored. In contrast to  single drug chemotherapy, the combined drugs treatment may show additive or  synergistic or antagonistic effects. The pharmaco-kinetics show spotentiative  or reductive responses with reference to the choice of drugs combination.<br>
2、the NPs are in a homogeneous medium
  &nbsp;&nbsp;&nbsp; For  example, the treatment of advanced breast cancer using paclitaxel and cisplatin  drug combinations indicated a high efficacy in overall response rate. In a  word, the combined chemotherapy strongly demands an efficient delivery vehicle  that can carry multiple cargos to the target site with less accumulation in the nontarget site so that the trade-off on dosage amount can be brought closer. A  mixed group of DNA origami has the potential to carry different types of drugs. </p>
 
  <hr>
The temperature increase on the surface of a spherical gold NP can be calculated by using the following equation.
<p class="js"><strong>C. Transport drugs to  tumor site precisely</strong></p>
 
</div>
[[Image:2014-08-18_201722.jpg]]
<div class="bq1" id="apDiv11"><img src="Tianjin_index13.png" width="45" height="45" align="absmiddle"><a name="design" id="design"></a><span class="bq3">※DESIGN</span></div>
 
<div class="js" id="apDiv12"> &nbsp;&nbsp; <span class="bq1">The  frequence that DNA is used as the engineering material of choice for the construction of nanoscale circuits, structures, and motors is much higher. Many  of these enzyme-free constructions function by DNA strand displacement  reactions.<br>
<big>Corrected equation of △T</big>
  </span><br>
 
  <strong>DNA strand displacement </strong><br>
The fact is that the particle is located close to the interface between two homogeneous media. They are lying on a glass substrate and immersed in water. So the equation has to be corrected by a correction factor b. And κ should be replaced by κeff = κ/b
  &nbsp;&nbsp;&nbsp; <span class="bq1">Strand  displacement means that one strand of DNA displaces another in binding to a  third strand with partial complementarity to both. It is highly desireable.<br>
 
  Strand displacement  is the process through which two strands with partial or full complementarity  hybridize to each other, displacing one or more pre-hybridized strands in the  process. Strand displacement can be initiated at complementary single-stranded  domains (referred to as toeholds) and progresses through a branch migration  process that resembles a random walk. By varying the strength (length and  sequence composition) of toeholds, the rate of strand-displacement reactions  can be quantitatively controlled over a factor of 10^6. Importantly, this  feature allows engineering control over the kinetics of synthetic DNA devices.<br>
[[Image:2014-08-18_201723.jpg]]
  &nbsp;&nbsp; In  molecular biology, strand displacement frequently denotes a process mediated by  enzymes such as polymerases, but the reaction as defined above is guided by the  biophysics of DNA and occurs independently of enzymes.&nbsp; Enzyme-free strand displacement and branch  migration have been studied since the 1970s, but have only been applied to DNA  nanotechnology within the past decade.   </span><br>
 
  <br>
r is the distance from the center of a particle. We want to calculate the temperature increase on the surface. So r= R, radius of a NP.
  <img width="554" height="204" src="wiki-2'_clip_image002_0002.jpg">
 
  <hr>
[[Image:2014-08-18_201908.jpg]]
<p><strong>Purpose</strong>
 
</p>
<big>Calculation of σabs</big>
  <p class="bq1">&nbsp;&nbsp; We use DNA sequence to connect the DNA  origami which is loaded with drugs with the Au nanoparticle. And then, on the one hand, the purpose and the function of this DNA sequence is to release the drugs after under certain temperature and will never be back to the  nanoparticle. And on the other hand, we hope that it can release different  drugs under different thermal condition.</p>
 
  <hr>
1、when R≤15nm
<span class="bq1"><br>
 
  </span><strong>Design </strong><br>
[[Image:2014-08-18_201931.jpg]]
  <strong>Inreversible release</strong><span class="bq1"><br>
 
  <br>
[[Image:2014-08-18_201951.jpg]]
  &nbsp;&nbsp;&nbsp;&nbsp; To make the  process of releasing drugs inreversible, we need to design a kind of DNA  sequence which will be inactive at the single state, while active when it is  complementary.</span><br>
 
  <span class="bq1">&nbsp;&nbsp;&nbsp; We find out the hairpin structure which  can exactly suit our idea.<br>
[[Image:2014-08-18_202005.jpg]]
  <img width="147" height="270" src="wiki-2'_clip_image005_0001.jpg" align="left" hspace="12">&nbsp;&nbsp; Because of the toehold&rsquo;s role in initiating strand displacement reactions, strands can be rendered effectively  unreactive if the toehold domain is made inaccessible by toehold sequestering. Toehold  sequestering can be achieved in a number of ways, the two most common of which  are hybridization of the toehold to a complementary domain and isolation of the  toehold in a short hairpin structure where helix formation is difficult. Programmed sequestering and subsequent exposure of toehold domains allows  precise control of order and timing over the reactions and has been used in  conjunction with toehold-mediated strand displacement to construct molecular motors,  polymerization reactions, catalytic reactions, and logic gates.</span>
 
  <hr>
[[Image:2014-08-18_202017.jpg]]
  <p><br>
 
    <strong>Multistage release<br>
[[Image:2014-08-18_202033.jpg]]
    </strong><br>
 
    <img width="217" height="164" src="wiki-2'_clip_image008_0000.jpg" align="left" hspace="12"><span class="bq1">&nbsp;&nbsp; To make the multistage release of the  design possible without more difficult steps, we decide to change the tm of the  complementary domain by change the length of one single strand which will be  connected with the DNA origami and drugs.</span><br>
2、when R>15nm
  </p>
 
  <p><span class="bq1">&nbsp;&nbsp;&nbsp; Like the figure strand A will be connected  with the DNA origami and strand B will combine with the Au nanoparticle.</span></p>
The previous formalism becomes inappropriate and the Mie theory has to be used. Within this model, the σabs is equal to
  <hr>
 
  &nbsp;<strong>Structure</strong><br>
[[Image:2014-08-18_202737.jpg]]
  <span class="bq1"><img src="wiki-2'_clip_image010_0000.jpg" width="127" height="180" hspace="12" align="top"></span>
 
  <p><span class="bq1">&nbsp;&nbsp;&nbsp; The hairpin  motif like figure comprises four concatenated domains, red yellow blue and  green. And two basic reactions can be programmed using this motif, as  illustrated for the example of catalytic duplex formation in this figure.</span></p>
[[Image:2014-08-18_202813.jpg]]
  <hr>
 
  <p><br>
[[Image:2014-08-18_202827.jpg]]
  <strong>Assemble</strong></p>
 
  <p><img src="untitled11.jpg" alt="" width="289" height="265"><br>
According to the formulas got above, the dependence amongst the intensity, wave length of the illumination, the size of the nanoparticle and the local temperature increase around a nanoparticle become quantative. Then we are able to select the light source needed for certain temperature increase. For instance, if we use a laser whose wave length is 520nm and intensity is 2.7×10<sup>5</sup>W/cm<sup>-2</sup> to irradiate a 40nm-gold nanoparticle, the local temperature of the nanoparticle will be 70°C.
    <span class="bq1">&nbsp;&nbsp;&nbsp; First, an  assembly reaction (1) occurs when a single-stranded initiator I, containing an  exposed toehold a*, nucleates at the exposed toehold a of  hairpin A, initiating a branch migration that opens the hairpin. Hairpin  domains yellow and blue were exposed, and can then serve as assembly initiators  for other suitably defined hairpins, permitting cascading (like B&rsquo;s hairpin).<br>
 
  &nbsp;&nbsp;&nbsp; Second, the same strand displacement  reaction (2) occurs between strand B and A to form the polymer A, B and I.<br>
==References==
  &nbsp;&nbsp;&nbsp; Third a disassembly  reaction (3) occurs when a single-stranded domain (yellow domain of B)  initiates a branch migration that displaces the initiator I from A. In this  example, I catalyses the formation of duplex A and B through a prescribed  reaction pathway.<br>
[1] Rajendran A, Endo M, Katsuda Y, et al. Programmed two-dimensional self-assembly of multiple DNA origami jigsaw pieces[J]. ACS nano, 2010, 5(1): 665-671.<br><br>
  &nbsp;&nbsp;&nbsp; And finally, the green domain of A and  the blue domain of B partially assemble and open the green hairpin of A. What&rsquo;s  more with the change of the length of the green domain of A, and let the blue  domain of B be always complementary to the loop of the green hairpin, then we  can make the purpose of multistage release.
[2] Huang X, Jain P K, El-Sayed I H, et al. Plasmonic photothermal therapy (PPTT) using gold nanoparticles[J]. Lasers in medical science, 2008, 23(3): 217-228.<br><br>  
    </span>&nbsp;<br>
[3] Weissleder R. A clearer vision for in vivo imaging[J]. Nature biotechnology, 2001, 19(4): 316-316. <br><br>
  </p>
[4] Pinheiro A V, Han D, Shih W M, et al. Challenges and opportunities for structural DNA nanotechnology[J]. Nature nanotechnology, 2011, 6(12): 763-772.<br><br>  
</div>
[5] Baffou G, Berto P, Bermúdez Ureña E, et al. Photoinduced Heating of Nanoparticle Arrays[J]. ACS nano, 2013, 7(8): 6478-6488.<br><br>  
<div id="apDiv13">
<html>
  <p class="js"><strong>Process of our drug  delivery system</strong></p>
  <ol>
    <li class="bq1">Apply magnetic field to transport drug carriers(DNA  origami) to tumor cells directly.</li>
    <li class="bq1">Use  light of low intensity to open DNA origami A and release drug A to kill tumor.</li>
    <li class="bq1">Use  light of high intensity to open DNA origami B and release drug B to kill tumor.
      <hr>
    </li>
  </ol>
  <p><span class="bq1"><br>
  &nbsp; 1.&nbsp; Drive  our DNA spaceship(DNA origami) to a specific planet(tumor cells)<br>
  &nbsp; 2.&nbsp; Use  light of low intensity to open our DNA spaceship, astronaut A(drug A) comes out  and lands on the planet.<br>
  &nbsp; 3.&nbsp; Use  light of high intensity to open our DNA spaceship, astronaut B(drug B) comes  out and lands on the planet.</span><br>
  <img src="wiki-2'_clip_image002_0000.jpg" alt="" width="434" height="239"></p>
  <p class="bq1">&nbsp;&nbsp;&nbsp; Because  our drug delivery system is similar to the real spaceship. Therefore, we termed the project&rdquo;DNA spaceship&rdquo;. </p>
  <hr>
</div>
<div id="apDiv14">&copy; COPYRIGHT  TJU BIOMOD TEAM 2014, ALL RIGHTS RESERVED</div>
<div id="apDiv16">
  <hr>
  <p><span class="js"><strong>Release</strong></span><br>
    <br>
  <span class="bq1">&nbsp;&nbsp; With different degrees of heat, the hydrogen bond between these two strands will be broken and the  two strands will be set apart and come back to form two hairpins and can never  combine any more.</span></p>
  <hr>
  <p><br>
    <span class="js"><strong>Logic</strong></span><br>
    <br>
    <span class="js"><img src="wiki-2'_clip_image017_0000.jpg" alt="" width="78" height="85" hspace="12" align="left"></span><img width="190" height="198" src="wiki-2'_clip_image019_0000.jpg" align="left" hspace="12"><span class="bq1">&nbsp;&nbsp; To assist in programming more complex  reaction pathways, we abstract the motif  as a node with four ports  like figure. The state of each port is either accessible (open triangle/circle) or  inaccessible (solid triangle/circle), depending on whether the toehold of the corresponding  motif domain is exposed or sequestered.<br>
    &nbsp;&nbsp;&nbsp; And the secondary reaction mechanism  can use this kind of way to express. </span>
  </p>
  <p class="js">&nbsp;</p>
  <p class="js">&nbsp;</p>
  <hr>
  <span class="js"><strong><br>
  How to open DNA  origami using light signal?</strong><strong></strong></span><strong><br>
  &nbsp; &nbsp; </strong><span class="bq1">This kind of  light control to open DNA origami is achieved by gold nanoparticles(AuNPs). AuNPs can turn light power into heat  power. AuNPs are attached to DNA origami  using DNA linkers. After optical stimulation, the AuNPs will locally generate  heat which breaks the DNA double strands that allow DNA origami to close. Thus  our DNA origami is opened and drug loaded inside is released. AuNPs are like  the keys to open the DNA door of origami.<br>
  <br>
  <img width="273" height="226" src="wiki-2'_clip_image002.jpg"><img width="286" height="167" src="wiki-2'_clip_image004.jpg"></span>
  <hr>
  <p>&nbsp;</p>
  <ol>
    <li class="js"><strong>Details  about properties of AuNPs</strong></li>
  </ol>
  <p class="bq1">&nbsp;&nbsp;&nbsp; Currently a  popular area in nanomedicine is the implementation of plasmonic nano-particles  for cancer diagnosis and photothermal therapy, attributed to the intriguing  optical properties of the nanoparticles. The surface plasmon resonance, a  unique phenomenon to plasmonic nanoparticles leads to strong electromagnetic  fields on the particle surface and consequently enhances all the radiative  properties such as absorption and scattering. <br>
  &nbsp;&nbsp;&nbsp; Plasmon-resonant nanoparticles (NPs) are generating much  enthusiasm due to their extraordinary optical properties, particularly in the  fields of life sciences and medicine. A special property of these  plasmon-resonant NPs is their heat generation upon excitation of the collective  electron resonance by a certain laser frequency. The determination of the  temperature of plasmon-resonant NPs appears essential for a number of different  applications.<br>
  &nbsp;&nbsp;&nbsp; Noble metal nanoparticles, especially gold nanoparticles (AuNPs), 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. Gold nanoparticles exhibit NIR activated  photothermal activity due to their geometry dependent plasmon resonance,  resulting from collective oscillation of surface electrons upon excitation with  light at the resonance frequency. Gold is also attractive because due to its  inertness , biocompatibility , low cytotoxicity and long history of medical  use.</p>
  <hr>
  <p class="bq1"><br>
    <span class="js">&nbsp; 2. <strong>We choose NIR laser as our light signal<br>
    </strong></span><br>
  &nbsp;&nbsp;&nbsp; In  recent years, the near infrared (NIR) laser (in the region of 650 to 1100 nm)  mediated photothermal ablation (PTA) therapy has attracted increased attentions  for effective cancer therapy. NIR laser irradiation can induce hyperthermia  damage of cancer cells and tumor organ with deep tissue penetration.  Additionally, PTA also possesses minimal invasiveness and precise  spatial-temporal selectivity in comparison with conventional therapeutic  modalities (i.e. surgical resection, radiotherapy and chemotherapy), since its  therapeutic effect happens only at the tumor site where both light-absorbent  and localized photo-irradiation coexist. Among various NIR absorbents reported  so far, gold nanocrystals (i.e. gold nanorods , gold nanoshells , and gold  nanocages et al.) were most extensively investigated due to their excellent  biocompatibility and tunable surface plasmon resonance (SPR) property to  convert NIR light into local heat.</p>
  <hr>
  <p class="js"><strong> How to open  different DNA origami selectively using light?</strong><br>
    &nbsp; &nbsp;  <span class="bq1">Temperature  increase of Au particle can be calculated. And the temperature increase of Au  particles is related to the intensity and wavelength of light as well as the  diameter of Au particles. Generally, if the other factors remain unchanged, the  more intense light we use, the hotter Au particles could be. We designed two  kinds of DNA origami. These two kinds of DNA origami have different DNA double  lock strands. And melting temperature of this two types of DNA lock strands is  different.<br>
    Initially  we use light of low intensity to irradiate Au nanoparticles. Correspondingly Au particles create a  low temperature increase. DNA lock strands of low melting temperature will  break. And DNA origami with lock strands of low melting temperature on it would  open and release drugs inside. <br>
    &nbsp;&nbsp;&nbsp; Next  we use light of high intensity instead. In the same way DNA origami with lock  strands of high melting temperature on it would open and release a different  kind of drugs inside. <br>
    &nbsp;&nbsp;&nbsp; Thus  with the help of Au nanoparticles we can open different DNA origamis and  release different drugs step by step.</span><br>
    <br>
  <img width="554" height="293" src="wiki-2'_clip_image005.jpg"></p>
  <hr>
  <span class="js"><strong>How to transport  drugs to tumor site precisely？</strong></span><br>
  <br>
  <span class="bq1">&nbsp;&nbsp;&nbsp; Usually anticancer drugs aren&rsquo;t targeted, which means  they will attack tumor as well as normal cells. To solve this problem, magnetic  nanoparticles(Fe3O4) are attached on our DNA origami to  control the transportation of the DNA origami more precisely. Thus with the  help of magnetic field, drugs can be transported to tumor site directly without  attacking normal cells.</span><br>
  <img width="303" height="289" src="wiki-2'_clip_image006.jpg">
<p class="bq1"><img src="untitled.jpg" alt="" width="363" height="278"></p>
<hr>
<p class="bq1">&nbsp;</p>
</div>
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  	            <li><a href='http://openwetware.org/wiki/Biomod/2014/wiki-2%27.html#background'><span>Background</span></a></li>
                   <li><a href='http://openwetware.org/wiki/Biomod/2014/wiki-2%27.html#motivation'><span>Motivation</span></a></li>
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Background

<html></a></html> DNA Origami

The unique structural motifs and molecular recognition properties of DNA make it a promising template for building nanostructures. Using a long single-stranded DNA as a template, a novel strategy, the so-called DNA origami method, has been developed for the preparation of various two-dimensional (2D) and three-dimensional (3D) nanostructures with defined size which is predictable, precise, controllable and efficient.

Fig 1.DNA origami and its applications.

DNA origami is an excellent plantform for the nanopatterning and a variety of functional biomolecules and nanoparticles 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 hetero-elements such as proteins and nanoparticles. Therefore, DNA origami has shown great potential in nanotechnology.

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.

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.

Fig 2.The photothermal property for gold nanoparticle.

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 light into local heat. Gold nanoparticles exhibit light 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.

Fig 3.The the therapy use of gold nanoparticle and DNA origami.


<html><a name="motivation"></html>

Motivation

<html></a></html>

DNA origami is also emerging as a strong candidate for drug delivery in living systems. For its high compatibility to so many kinds of molecules, such as functional biomolecules and nanoparticles which can be linked to the DNA origami scaffolds, to obtain complicated functional nano-devices. Besides, it's capability to fold structures of 2-dimentional or 3-dimentional makes it will get more circumstances to apply. What’s more, the high rate of development and the endless potential of DNA origami make it worth researching.

But the methods of opening an origami box or changing the structure of it is limited in the addition of ssDNA to open by strand replacement or chemical methods to break, which limits the applications of origami especially in vivo. So, a physical way without adding anything to achieve the goal is what we need and search for. We choose light. But why?

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 for therapeutic could cause less damage on tissue.

In fact, in treatment, only light will produce sufficient power to penetrate the specific site with less energy loss. And, light has already been used into medical treatment field for many years, such as photothermal therapy. Then, the next question is how to change the light into heat, and the traditional way of photothermal therapy may answer this question.

A type of nanomaterial with strong light absorption comes into the sight of us, which is named gold nanoparticle (Au NP). Au NP has immense potential for the selective laser photothermal therapy of cancer cells due to its photo-thermal activity. It can convert light into heat, and leads to a temperature increase, which serves as our opening trigger.

And as all we know, origami is locked by complementary DNA sequence, which is difficult to totally separate by heating and restoring to room temperature. So that means our origami box have a large possibility to reclose after its open. To overcome this problem, we design three-arm DNA lock to “intelligently” control the open and close of origami by displacement, and it will be showed in the next part.

All in all, by creating and utilizing these principle or design, we want to grant this device with the following control characteristics: Local release of drugs. Traditional drugs are transported to every corner in human body, and may attack all the cells including the normal ones,such as the low specificity of anticancer drugs. However, our device is supposed to release at a specific location in human body under control.


Selective release of drugs

We want to give our device a DNA logical gate, which enable the device to selectively release specific drugs aimed at curing different cells under different conditions.

Physical control

We replace traditional control methods of adding chemicals with a physical trigger to make our device tunable for future modification, which has never done before.


<html><a name="calculation"></html>

Calculation

<html></a></html> Equation of △T

WHEN

1、the NPs are far enough（ interdistance is at least 4 or 5 times larger than the NP diameter ）

2、the NPs are in a homogeneous medium

The temperature increase on the surface of a spherical gold NP can be calculated by using the following equation.

Corrected equation of △T

The fact is that the particle is located close to the interface between two homogeneous media. They are lying on a glass substrate and immersed in water. So the equation has to be corrected by a correction factor b. And κ should be replaced by κeff = κ/b

r is the distance from the center of a particle. We want to calculate the temperature increase on the surface. So r= R, radius of a NP.

Calculation of σabs

1、when R≤15nm

2、when R>15nm

The previous formalism becomes inappropriate and the Mie theory has to be used. Within this model, the σabs is equal to

According to the formulas got above, the dependence amongst the intensity, wave length of the illumination, the size of the nanoparticle and the local temperature increase around a nanoparticle become quantative. Then we are able to select the light source needed for certain temperature increase. For instance, if we use a laser whose wave length is 520nm and intensity is 2.7×105W/cm-2 to irradiate a 40nm-gold nanoparticle, the local temperature of the nanoparticle will be 70°C.

References

[1] Rajendran A, Endo M, Katsuda Y, et al. Programmed two-dimensional self-assembly of multiple DNA origami jigsaw pieces[J]. ACS nano, 2010, 5(1): 665-671.

[2] Huang X, Jain P K, El-Sayed I H, et al. Plasmonic photothermal therapy (PPTT) using gold nanoparticles[J]. Lasers in medical science, 2008, 23(3): 217-228.

[3] Weissleder R. A clearer vision for in vivo imaging[J]. Nature biotechnology, 2001, 19(4): 316-316.

[4] Pinheiro A V, Han D, Shih W M, et al. Challenges and opportunities for structural DNA nanotechnology[J]. Nature nanotechnology, 2011, 6(12): 763-772.

[5] Baffou G, Berto P, Bermúdez Ureña E, et al. Photoinduced Heating of Nanoparticle Arrays[J]. ACS nano, 2013, 7(8): 6478-6488.

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