Biomod/2014/Kashiwa/Project: Difference between revisions

From OpenWetWare
Jump to navigationJump to search
No edit summary
No edit summary
 
(144 intermediate revisions by 2 users not shown)
Line 6: Line 6:
<style type="text/css">
<style type="text/css">


div.imagebox {
  border: 1.7px dashed #2E2EFE; /* 1.枠線 */
  background-color: #F0F8FF;  /* 2.背景色 */
  width: auto; /* 横幅 */
  float: right; /* 右に配置 */
  margin: 0px 30px 0px 10px;
}
div.leftbox {
  border: 1.7px dashed #2E2EFE; /* 1.枠線 */
  background-color: #F0F8FF;  /* 2.背景色 */
  width: auto; /* 横幅 */
  float: left; /* 右に配置 */
  margin: 0px 10px 0px 30px;
}
p.cap{
font-size:85%;
}
p.image {
  text-align: center;
  width: auto;
  height: auto;
  margin: 5px;
}
p.caption {
  margin: 5px 10px;
  font-size: 90%;  /* 5.文字サイズ */
  color: black; /* 6.文字色 */
}
</style>
</style>
</head>
</head>
Line 11: Line 41:
<body>
<body>
<a name="1"></a>
<a name="1"></a>
<font face="Futura,Arial,Frutiger" font size="24pt">PROJECT</font>
<font face="Futura,Arial,Frutiger" font size="24px">PROJECT</font>
<br>
<br>
<br>
Artificial immune system for cancer cells
<br>
<br>
<h1 class="title"><a name="background">&nbsp;Background</a></h1>
<h1 class="title"><a name="background">&nbsp;Background</a></h1>
Immunotherapies against cancer attracts attentions as an effective way to kill tumors. In 2011, Ralph Steinman received Novel prize for his discovery of dendritic cells and its role in adaptive immunity which can be used for the cancer immunotherapy.
<p class="paragraph">Cancer is a group of diseases characterized by uncontrolled cellular proliferation and invasion into bodily tissues and organs. One of the most common causes of mortality, it accounts for about 13 percent of human death in the world. </p>
<br>
<br>
<font style="font-size:32px;">&nbsp;&nbsp;<i>Modern Cancer Treatments</i></font>
<br>
<br>
<font size="14pt"> What is cancer immunotherapy?</font>
<p class="paragraph">Surgery, radiotherapy, and chemotherapy are the three major treatments to cure cancers used by oncologists. The most popular one, chemotherapy, uses chemical drugs that kill cancer cells, and it is the only systemic therapy among the three. Chemotherapy, however, can cause serious side effects because anti-cancer drugs can affect normal cells as well. In order to increase the specificity to cancer cells, drug delivery systems (DDS) have been widely studied by scientists.</p>
<br>
<br>
Cancer immunotherapy induces the immune system to reject and destroy tumors.
<font style="font-size:32px;">&nbsp;&nbsp;<i>Drug Delivery Systems</i></font>
<br>表：Merits Problems
<br>(Merits)
<br>(Problems)Induced immune cells that are cultured in vitro(italic) cannot reproduce in patients' bodies and have very short life length.(具体的な時間を教えてください)
<br> Culturing immune cells in vitro(italic) takes time.(具体的な時間を教えてください)
<br> (Concerns about effects on a patient's natural immune system.(実際に問題としてあるか調べる))
<br>The first problem of a irreproducibility can be solves using stem cells such as iPS cells (induced pluripotency stem cells)  by stimulating the differentiation to the specific T lymphocytes. However, establishment of the stem cells and differentiation to T-cells in vitro(italic) are troublesome and time-costly as the treatment is patient-specific and the differentiated T-cells are fragile.
<br>
<br>
<h1 class="title"><a name="background">&nbsp;Motivation</a></h1>
<p class="paragraph">DDS is a general term for various ways to deliver drugs selectively to pathogens while avoiding normal cells. Although DDS is a promising strategy, one drawback is that most DDS rely on diffusion to deliver drugs, which limits their mobility and delivering effectiveness. With diffusional DDS, for example, we cannot deliver drugs to tumors that are away from their diffusion paths. Defective drug delivery to any single cancer cell is a crucial problem for the cancer treatments because any remaining cancer cells can reproduce or metastasize, and cause recurrence of the disease.<a name="2">&nbsp;</a></p>
 
<br>
<br>
In order to overcome the pre-stated problems, we want to build more artificial immune system that is less fragile, more general, (and function independently with the patient's natural immune system)(上の3.の問題がなかったら消す).
<br>We proposal our artificial liposomal immune system (ALIS)
                robotic immune cell (RICe) to satisfy the following components in order to mimic the mammalian immune system:
<br>1. It can be activated by outside stimulus such as ultrasound. In our in vitro(italic) experiment, we use thrombin as an external signal.
<br>2. Once activated, it starts patrolling the blood vessels to find cancer markers.
<br>3. As it senses cancer, it releases anti-cancer drug such as taxol.
<br>
<br>
<br>We decide to fucus on #1 and #2 as our study this summer.
<h1 class="title"><a name="background">&nbsp;Motivation</a></h1>
<br>We plan to achieve #1 by developing a receptor that recognize the outside signal.
<br>We plan to achieve #2 by developing an actin-like monomer that polymerizes in one end and depolymerizes on the other end to allow mobilization.
<br>Both the receptor and the actin-like monomer will be designed using DNA origami.
<br>
<br>
<font style="font-size:32px;">&nbsp;&nbsp;<i>Creating a New Way of Delivery</font> <font style="font-size:20px;"> - self-mobile, effective DDS</i></font>
<br>
<br>
* What is good about RICe?
 
<br>白い、美味い、低カロリー
<div class="imagebox">
<br>(表：既存テーマ比べて今テーマの秀でている点)
<p class="image"><img src="http://openwetware.org/images/f/f6/Police_vs_DDS.png" width="300px" height="175px"></p>
<p class="caption">Fig.1. Difference between ordinary DDS and PoLICe.</p>
</div>
 
<p class="paragraph">The problem with the traditional DDS is its lack of active mobility. In order to overcome this, we decided to build a patrolling nano-robot which moves not only by diffusion but also by self-propulsion to transfer drugs away from their diffusion paths. Moreover, nano-scale movements of the robot enable cell-by-cell analysis in DDS with implemented cancer sensors on its surface, enabling the system to inspect cancer cells at single-cell resolution.</p>
<br clear="right">
 
<br>
<br>
* Why using DNA origami?
<font style="font-size:32px;">&nbsp;&nbsp;<i>Strategy of the Self-Moving Robot</i></font>
<br>
<br>
DNA origami is the folding of DNA to build customized nano-scale shapes or structures.
<p class="paragraph">To make the nano-robot, we drew inspiration from a dendritic immune cell, which moves in a body by migration. Dendritic cells have spines that are small actin-rich protrusions; by remodeling (polymerizing and depolymerizing) actin filaments inside, they can change their shapes and migrate.</p>
<br>Using DNA origami, it becomes easy to control the size and structure of the actin-like monomer. This gives advantages such as:
<p class="paragraph">Based on this idea, we developed actin-like monomers (named “Motor-Monomers”) and put them into a liposome equipped with a starter switch (named “Receptor”). When the Receptor recognizes an outside signal, such as a cancer marker, the Motor-Monomers start polymerizing to form the Motor-Polymer. The Motor-Polymer should polymerize in one end and de-polymerize in the other end to move toward a specific direction, mimicking the actin filaments.</p>
<br>1. The large monomer size can reduce the number of the monomers used to have effective mobility.
<p class="paragraph">As we modeled this polymerizing-in-a-liposome system based on a dendritic immune cell, we named it "<b>Polymeric and Liposomal Immune Cell (PoLICe)</b>."<a name="3">&nbsp;</a></p>
<br>2. Precise construction of the monomer shape can allow the accurate simulation of the RICe movements.
 
<br>As for the signal receptor, the control of the controllability of the DNA origami may allow the following advantages:
<br>1. Not only the pure mimic of the currently known membrane protein structures, but also the new structures that can sense the new signals not sensed by the natural membrane proteins.
<br>2.It can build a mechanism to release the patrolling signal.
<br>3.(根拠は？)It may have lower background noise by controlling the precise structures of on- and off- states.
<br>4.(金属？金属イオン？金属イオンの場合はzinc fingerなどあるが、膜たんぱく質に組みこめなくてDNA origamiに組み込める根拠があると参考文献として掲載したい。イミフなので翻訳したくないぶー。)
<br>
<br>
<a name="2"></a>
<br>
<br>
<br>
<br>
<h1 class="title"><a name="background">&nbsp;Project Goals</a></h1>
<p class="paragraph">As a first stage of building PoLICe, we aimed to <b>achieve a simple deformation of a liposome after given stimulus</b>. The components of the simple PoLICe can be separated into three parts.</p>
<center>
<table align="left" style="margin:5px;">
<tr>
<th><img src="http://openwetware.org/images/c/c5/Project1Kashiwa.png" width="175px" height="200px"></th>
<th><img src="http://openwetware.org/images/c/c9/Project2Kashiwa.png" width="175px" height="200px"></th>
<th><img src="http://openwetware.org/images/a/ad/Project3Kashiwa.png" width="175px" height="200px"></th>
<th><img src="http://openwetware.org/images/4/46/Project4Kashiwa.png" width="200px" height="190px"></th>
</tr>
<tr>
<td>
<p class="cap">Fig.2. PoLICe before recognition of outside signal.</p></td> <td> <p class="cap">Fig.3. The Motor gets activated upon recognition of outside signal.</p></td>
<td><p class="cap">Fig.4. Polymerization of the Motor-Monomers.</p></td><td><p class="cap">Fig.5. Deformation of liposome.</p></td>
</div></tr>
</table></center>
<p class="paragraph">First, we need to develop a sensing system, called Receptor, which works as a starter switch of the Motor, so that we can control the onset of PoLICe patrolling. The Receptor is designed to be embedded across a liposomal membrane, where it reacts with the outside signals in the extra-liposomal domain and activates the Motor-Monomers to polymerize within the intra-liposomal domain.</p>
<br clear="right">
<p class="paragraph">Second, we need to develop a polymer-based moving system which works as the motor of the PoLICe. In order to achieve the system, we planned to put Motor-Monomers into the liposome at the deactivated state and start polymerization when the Receptor switches on.</p>
<p class="paragraph">Finally, we need to connect two systems with each other and experimentally verify the deformation of the liposome.</p>
<br clear="right">
<br>
<br>
<a name="Goals"><h1 class="title"><a name="Goals">&nbsp;Goals</a></h1>
<center>
<img src="http://openwetware.org/images/e/e0/Goal.png" width="800px" height="330px">
</center>
<br>
<br>
<br>
<br>
<h2 class="reference">Reference</h2>
<p class="reference">1.All Cancer (excluding non-melanoma skin cancer) Estimated Incidence, Mortality and Prevalence Worldwide in 2012 from International Agency for Research on Cancer website; http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx</p>
</body>
</body>


Latest revision as of 00:54, 26 October 2014

<html> <head> <div id="#top"></div>

<script type="text/javascript" src="http://code.jquery.com/jquery-1.9.1.min.js"></script>

<script type="text/javascript"> new Image(120,80) = "http://openwetware.org/images/7/7a/Logo2Kashiwa.png";

new image(120,80) = "http://openwetware.org/images/1/1d/Logo2.5.png";

new image(71,143) = "http://openwetware.org/images/2/2a/Top1.gif";

new image(71,143) = "http://openwetware.org/images/f/f0/Top2.gif";

new image() = "http://openwetware.org/images/3/38/BackgroundKashiwa.png";

new image() = "http://openwetware.org/images/9/9c/BackgroundKashiwa2.png"; </script>


<script type="text/javascript"> 

  $(function(){
     $("#menu li").hover(function(){
        $("ul",this).show();
     },
     function(){
        $("ul",this).hide();
     });
  });

</script>


<script type="text/javascript"> <!-- if (document.images) {

// 設定開始（使用する画像を設定してください）

// 通常の画像 var img0 = new Image(120,80); img0.src = "http://openwetware.org/images/e/ec/LogoKashiwa.png";

// ポイント時の画像1 var img1 = new Image(120,80); img1.src = "http://openwetware.org/images/2/26/Logo3Kashiwa.png";


// 設定終了

} // ポイント時の処理 function On(name) { if (document.images) { document.images['def'].src = eval(name + '.src'); } } // 放した時の処理 function Off() { if (document.images) { document.images['def'].src = img0.src; } } // --> </script>

<META http-equiv="Content-Style-Type" content="text/css">

<style type="text/css">


.page-back { position: fixed; bottom: 25px; right: 25px;}

p.paragraph { 

 font-size :100%;
 line-height: 135%;
 margin: 10px 25px;

}

p.reference { 

 font-size :90%;
 line-height: 135%;
 margin: 10px 20px;

}

p.indent-paragraph { 

 font-size :110%;
 line-height:1.5;
 margin:0 30px;
 text-indent: 1em;
 }

h1.title a{ 

 font-size :100%;
 display: block;
 text-decoration: none;
 color: #000000;

　font-weight:bolder; 

 border-left: solid 5px #e00000;
 }

h2.reference a{ 

 font-size :90%;
 display: block;
 text-decoration: none;
 border-left: solid 5px;
 }

body { 

 font-size: 12px;
 font-family: Frutiger, Helvetica, Arial;
 background-color: #B5D3FF;
 overflow-y:scroll;
 overflow-x:hidden;

} article { 

 background-color: #ffffff

} .container { 

  background-color: #ffffff;
  margin-top:0px

}

.OWWNBcpCurrentDateFilled {display: none;}

}

  1. column-content

{ 

  width: 0px;
  margin: 0;
  padding: 0;
  float:left;

} .firstHeading { 

  display:none;
  width:0px;

}

  1. globalWrapper

{ 

  width:900px;
  background-color: #ffffff;
  margin-left: auto;
  margin-right: auto;

}

  1. column-one

{ 

  display:none;
  width:0px;
  background-color: #ffffff;

}

  1. content

{ 

  margin: 0px;
  align: center;
  padding: 0px 12px;
  width:876px;
  border: 0;

}

  1. bodyContent

{ 

  width: 800px;
  padding: 0px 38px;
  align: center;
  background-color: #ffffff;
  position:relative;

}

  1. column-content

{ 

  width: 900px;
  background-color: #ffffff;

}


  1. footer

{ 

  position: center;
  width: 900px;

}

div.menubar { 

  position: fixed;
  background-color: none; /* バーの背景色 */
  opacity: 0.95;
  border-top: 0px double white; /* バーの上端線 */
  border-bottom: 0px double white; /* バーの下端線 */
  min-width: 900px; /* メインメニュー全部が収まる最低横幅 */
  z-index:3

}

div.menubar ul#menu { 

  margin: -33px 0px 0px -50px; /* メニューバー外側の余白 */
  padding: 0px; /* メニューバー内側の余白 */
  height: 80px; /* メニューバーの高さ */
  list-style-type: none;

}

div.menubar ul#menu li { 

  min-width: 110px; /* メニュー項目の横幅 */
  height: 80px; /* メニュー項目の高さ(「メニューバーの高さ」と一致させる) */ 
  float: left;
  list-style-type: none;
  list-style-image: none;
  position: relative;

}

div.menubar ul#menu a { 

  text-decoration: none; /* メニュー項目の装飾(下線を消す) */
  display: block; 
  background-color: #1F003E;/* メニュー項目の背景色 */
  color: white; /* メニュー項目の文字色 */
  line-height: 80px; /* メニュー項目のリンクの高さ(「メニュー項目の高さ」と一致させる) */
  text-align: center; /* メインメニューの文字列の配置(中央寄せ) */　
  width: 100%;
  height: 100%;

}

div.menubar ul#menu a:hover { 

  background-image: url("http://openwetware.org/images/3/38/BackgroundKashiwa.png"); /* メニュー項目にマウスが載ったときの背景色 */
  color: #8B008B; /* メニュー項目にマウスが載ったときの文字色 */

}

div.menubar ul#menu a:active { 

  background-image: url("http://openwetware.org/images/3/33/Background2.png"); /* メニュー項目にマウスが載ったときの背景色 */
  color: #8B008B; /* メニュー項目をクリックした時の文字色 */

}

/* メニューバー直後のClearfix */ div.menubar ul#menu { 

  zoom:1;

} div.menubar ul#menu:after { 

  height: 0; visibility: hidden; content: "."; display: block; clear: both;

}

div.menubar ul#menu ul.sub { 

  background-color: #1F003E; /* サブメニュー全体の背景色 */
  border-width: 0px 0px 0px 0px; /* サブメニュー全体の枠線の太さ */
  border-style: solid; /* サブメニュー全体の枠線の線種 */
  border-color: #191970; /* サブメニュー全体の枠線の色 */
  margin: 0px;
  padding: 0px;
  display: none;
  position: absolute;

}

div.menubar ul#menu ul.sub li { 

  width: 110px;
  height: 50px; /* サブメニュー1項目の高さ */
  border-width: 0px 0px 0px 0px; /* サブメニュー1項目の枠線の太さ */
  border-style: solid; /* サブメニュー1項目の枠線の線種 */
  border-color: #191970; /* サブメニュー1項目の枠線の色 */
  z-index: 3

}

div.menubar ul#menu ul.sub li a { 

  line-height: 50px; /* サブメニュー1項目の行の高さ(「サブメニュー1項目の高さ」と合わせる) */
  text-align: center;  /* サブメニュー1項目の項目名の配置(中央寄せ) */
  text-indent: 0px;  /* サブメニュー1項目の項目名前方の余白 */

}

div.menubar ul#menu ul.sub li a:hover { 

  background-image: ('back');
  background-size: 100% auto;
  background-color: #FF00FF; /* サブメニュー項目にマウスが載ったときの背景色 */
  color:  #8B008B; /* サブメニュー項目にマウスが載ったときの文字色 */

}

div.menubar ul#menu ul.sub li a:active { 

  background-image: ('backclick') /* メニュー項目にマウスが載ったときの背景色 */
  backround-size: 100% auto;
  color: #8B008B; /* メニュー項目をクリックした時の文字色 */

}

</style>

<div class="menubar"> 

 <ul id="menu">
 <font face="Frutiger,Helvetica,Arial">
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa"><img src="http://openwetware.org/images/e/ec/LogoKashiwa.png" onmouseover="this.src='http://openwetware.org/images/7/7a/Logo2Kashiwa.png'" onclick="this.src='http://openwetware.org/images/1/1d/Logo2.5.png'" onmouseout="this.src='http://openwetware.org/images/e/ec/LogoKashiwa.png'" height="80px" width="120px" name="def"></a>
   </li>
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Project" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">PROJECT</span></a>
     <ul class="sub">
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Project#1" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Background</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Project#2" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Motivation</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Project#3" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Project Goals</span></a></li>
     </ul>
   </li>
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Trial" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">&nbsp;EARLY TRIAL&nbsp;</span></a>
     <ul class="sub">
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Trial#1" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Design</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Trial#2" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Approaches</span></a></li>
     </ul>
   </li>
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Design" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">DESIGN</span></a>
     <ul class="sub">
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Design#2" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">The Receptor</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Design#1" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">The Motor</span></a></li>
     </ul>
   </li>
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Highlights" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">&nbsp;EXPERIMENT&nbsp;&nbsp;</span></a>
     <ul class="sub">
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Highlights" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Highlights</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Receptor" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">The Receptor</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Motor" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">The Motor</span></a></li>
     </ul>
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Discussion" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">&nbsp;&nbsp;DISCUSSION&nbsp;</span></a>
     <ul class="sub">
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Discussion#1" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Achievements</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Discussion#2" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Future</span></a></li>
     </ul>
   </li>
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Protocols" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">PROTOCOL</span></a>
   </li>
   <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Team" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">TEAM</span></a>
     <ul class="sub">
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Team#1" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Members</span></a></li>
       <li><a href="http://openwetware.org/wiki/Biomod/2014/Kashiwa/Team#2" onMouseOver="On('img1')" onMouseOut="Off()"><span style="font-size:12pt;">Sponsors</span></a></li>
     </ul>
   </li>
 </font>
 </ul>

</div> <br> <br> <br> <div class="page-back"><a href="#top"> <img src="http://openwetware.org/images/2/2a/Top1.gif" onmouseover="this.src='http://openwetware.org/images/f/f0/Top2.gif'" onmouseout="this.src='http://openwetware.org/images/2/2a/Top1.gif'" height="150px"/></a></div> </head>


</html>

<html>

<head> <style type="text/css">

div.imagebox { 

  border: 1.7px dashed #2E2EFE; /* 1.枠線 */
  background-color: #F0F8FF;  /* 2.背景色 */
  width: auto; /* 横幅 */
  float: right; /* 右に配置 */
  margin: 0px 30px 0px 10px;

} div.leftbox { 

  border: 1.7px dashed #2E2EFE; /* 1.枠線 */
  background-color: #F0F8FF;  /* 2.背景色 */
  width: auto; /* 横幅 */
  float: left; /* 右に配置 */
  margin: 0px 10px 0px 30px;

}

p.cap{ 

font-size:85%;

}

p.image { 

  text-align: center;
  width: auto;
  height: auto;
  margin: 5px;

} p.caption { 

  margin: 5px 10px;
  font-size: 90%;  /* 5.文字サイズ */
  color: black; /* 6.文字色 */

} </style> </head>

<body> <a name="1"></a> <font face="Futura,Arial,Frutiger" font size="24px">PROJECT</font> <br> <br> <h1 class="title"><a name="background">&nbsp;Background</a></h1> <p class="paragraph">Cancer is a group of diseases characterized by uncontrolled cellular proliferation and invasion into bodily tissues and organs. One of the most common causes of mortality, it accounts for about 13 percent of human death in the world. </p> <br> <font style="font-size:32px;">&nbsp;&nbsp;<i>Modern Cancer Treatments</i></font> <br> <p class="paragraph">Surgery, radiotherapy, and chemotherapy are the three major treatments to cure cancers used by oncologists. The most popular one, chemotherapy, uses chemical drugs that kill cancer cells, and it is the only systemic therapy among the three. Chemotherapy, however, can cause serious side effects because anti-cancer drugs can affect normal cells as well. In order to increase the specificity to cancer cells, drug delivery systems (DDS) have been widely studied by scientists.</p> <br> <font style="font-size:32px;">&nbsp;&nbsp;<i>Drug Delivery Systems</i></font> <br> <p class="paragraph">DDS is a general term for various ways to deliver drugs selectively to pathogens while avoiding normal cells. Although DDS is a promising strategy, one drawback is that most DDS rely on diffusion to deliver drugs, which limits their mobility and delivering effectiveness. With diffusional DDS, for example, we cannot deliver drugs to tumors that are away from their diffusion paths. Defective drug delivery to any single cancer cell is a crucial problem for the cancer treatments because any remaining cancer cells can reproduce or metastasize, and cause recurrence of the disease.<a name="2">&nbsp;</a></p>

<br> <br> <h1 class="title"><a name="background">&nbsp;Motivation</a></h1> <br> <font style="font-size:32px;">&nbsp;&nbsp;<i>Creating a New Way of Delivery</font> <font style="font-size:20px;"> - self-mobile, effective DDS</i></font> <br>

<div class="imagebox"> <p class="image"><img src="http://openwetware.org/images/f/f6/Police_vs_DDS.png" width="300px" height="175px"></p> <p class="caption">Fig.1. Difference between ordinary DDS and PoLICe.</p> </div>

<p class="paragraph">The problem with the traditional DDS is its lack of active mobility. In order to overcome this, we decided to build a patrolling nano-robot which moves not only by diffusion but also by self-propulsion to transfer drugs away from their diffusion paths. Moreover, nano-scale movements of the robot enable cell-by-cell analysis in DDS with implemented cancer sensors on its surface, enabling the system to inspect cancer cells at single-cell resolution.</p> <br clear="right">

<br> <font style="font-size:32px;">&nbsp;&nbsp;<i>Strategy of the Self-Moving Robot</i></font> <br> <p class="paragraph">To make the nano-robot, we drew inspiration from a dendritic immune cell, which moves in a body by migration. Dendritic cells have spines that are small actin-rich protrusions; by remodeling (polymerizing and depolymerizing) actin filaments inside, they can change their shapes and migrate.</p> <p class="paragraph">Based on this idea, we developed actin-like monomers (named “Motor-Monomers”) and put them into a liposome equipped with a starter switch (named “Receptor”). When the Receptor recognizes an outside signal, such as a cancer marker, the Motor-Monomers start polymerizing to form the Motor-Polymer. The Motor-Polymer should polymerize in one end and de-polymerize in the other end to move toward a specific direction, mimicking the actin filaments.</p> <p class="paragraph">As we modeled this polymerizing-in-a-liposome system based on a dendritic immune cell, we named it "<b>Polymeric and Liposomal Immune Cell (PoLICe)</b>."<a name="3">&nbsp;</a></p>

<br> <br> <h1 class="title"><a name="background">&nbsp;Project Goals</a></h1> <p class="paragraph">As a first stage of building PoLICe, we aimed to <b>achieve a simple deformation of a liposome after given stimulus</b>. The components of the simple PoLICe can be separated into three parts.</p>

<center> <table align="left" style="margin:5px;"> <tr> <th><img src="http://openwetware.org/images/c/c5/Project1Kashiwa.png" width="175px" height="200px"></th> <th><img src="http://openwetware.org/images/c/c9/Project2Kashiwa.png" width="175px" height="200px"></th> <th><img src="http://openwetware.org/images/a/ad/Project3Kashiwa.png" width="175px" height="200px"></th> <th><img src="http://openwetware.org/images/4/46/Project4Kashiwa.png" width="200px" height="190px"></th> </tr> <tr> <td> <p class="cap">Fig.2. PoLICe before recognition of outside signal.</p></td> <td> <p class="cap">Fig.3. The Motor gets activated upon recognition of outside signal.</p></td> <td><p class="cap">Fig.4. Polymerization of the Motor-Monomers.</p></td><td><p class="cap">Fig.5. Deformation of liposome.</p></td> </div></tr> </table></center>

<p class="paragraph">First, we need to develop a sensing system, called Receptor, which works as a starter switch of the Motor, so that we can control the onset of PoLICe patrolling. The Receptor is designed to be embedded across a liposomal membrane, where it reacts with the outside signals in the extra-liposomal domain and activates the Motor-Monomers to polymerize within the intra-liposomal domain.</p> <br clear="right">

<p class="paragraph">Second, we need to develop a polymer-based moving system which works as the motor of the PoLICe. In order to achieve the system, we planned to put Motor-Monomers into the liposome at the deactivated state and start polymerization when the Receptor switches on.</p> <p class="paragraph">Finally, we need to connect two systems with each other and experimentally verify the deformation of the liposome.</p> <br clear="right"> <br> <br> <br> <h2 class="reference">Reference</h2> <p class="reference">1.All Cancer (excluding non-melanoma skin cancer) Estimated Incidence, Mortality and Prevalence Worldwide in 2012 from International Agency for Research on Cancer website; http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx</p> </body>

<footer style="position:relative; left:600px;"> <small> &copy; 2014 UTokyo Chem & Bio </small> </footer>

</html>

Retrieved from "https://openwetware.org/mediawiki/index.php?title=Biomod/2014/Kashiwa/Project&oldid=837678"