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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/micad/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-micad-lrg.png" alt="Cover of Molecular Imaging and Contrast Agent Database (MICAD)" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>Molecular Imaging and Contrast Agent Database (MICAD) [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK23367_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK23367_dtls__"><div>Bethesda (MD): <a href="https://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>; 2004-2013.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/micad/">Contents</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/micad/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/SPIO_alginate/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/PEG-S-Au-SPIO/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK23367_"><span class="title" itemprop="name">Thermally cross-linked superparamagnetic iron oxide nanoparticle-A10 RNA aptamer-doxorubicin conjugate</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">TCL-SPION-Apt(Dox)</div><p class="contrib-group"><span itemprop="author">Huiming Zhang</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK23367_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK23367_ai__"><div class="contrib half_rhythm"><span itemprop="author">Huiming Zhang</span>, PhD<div class="affiliation small">
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National Center for Biotechnology Information, NLM, NIH, Bethesda, MD,
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<span class="before-email-separator"></span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@dacim" class="oemail">vog.hin.mln.ibcn@dacim</a>
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</div></div></div><p class="small">Created: <span itemprop="datePublished">August 29, 2008</span>; Last Update: <span itemprop="dateModified">October 8, 2008</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="TCLSPIONAptDox.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK23367/table/TCLSPIONAptDox.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__TCLSPIONAptDox.T1_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Chemical name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Thermally cross-linked superparamagnetic iron oxide nanoparticle-A10 RNA aptamer-doxorubicin conjugate</td><td rowspan="9" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Abbreviated name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TCL-SPION-Apt(Dox)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Synonym:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Agent category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nucleic acid (nanoparticle)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Target:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Prostate-specific membrane antigen (PSMA)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Target category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nucleic acid binding protein</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Method of detection:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Magnetic resonance imaging (MRI), optical imaging</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Source of signal/contrast:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Iron oxides, doxorubicin-RNA complex</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Activation:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Studies:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul class="simple-list"><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" />
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<i>In vitro</i>
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</div></li></ul>
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<ul class="simple-list"><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
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</div></li></ul>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No structure is currently available in <a href="http://pubchem.ncbi.nlm.nih.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubChem</a>.</td></tr></tbody></table></div></div><div id="TCLSPIONAptDox.Background"><h2 id="_TCLSPIONAptDox_Background_">Background</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=TCL+SPION%20+%20Apt%20+%20Dox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein with a molecular weight of ~100 kDa (<a class="bk_pop" href="#TCLSPIONAptDox.REF.1">1</a>). PSMA is composed of several domains, including a potential phosphorylation site in the cytoplasmic tail (amino acids 1–18), a highly hydrophobic α-helix in the transmembrane region (amino acids 19–43), and catalytic sites in the extensive extracellular domain (amino acids 44–750). Two unique enzymatic functions are found in PSMA: <i>N</i>-acetylated, α-linked, dipeptidase (NAALADase) activity and folate hydrolase activity. As a prostate cancer cell (PCa) marker, PSMA expression is primarily prostate-specific (~100% in androgen-independent PCa cells), with very low levels (~1,000-fold less) in the brain, salivary glands, and small intestine. Thus, PSMA has become an excellent target for imaging and therapy.</p><p>Aptamers (from the Latin <i>aptus</i>, to fit, and the Greek <i>meros</i>, part or region) are single-stranded or double-stranded oligonucleotides (RNA or DNA, respectively) that are modified to bind a variety of targets with high binding affinity and specificity (<a class="bk_pop" href="#TCLSPIONAptDox.REF.2">2</a>). Aptamers range in size from 20 to 80 base pairs (~6–26 kDa) with dissociation constants in the range of 10 pM to 10 nM (<a class="bk_pop" href="#TCLSPIONAptDox.REF.3">3</a>). Unlike linear oligonucleotides, which contain genetic information or antisense oligonucleotides that interrupt the transcription of genetic information, aptamers are globular molecules with a shape similar to tRNA and bind to target proteins specifically (<a class="bk_pop" href="#TCLSPIONAptDox.REF.4">4</a>). A10 RNA aptamer (Apt) is a nuclease-stabilized 2’-fluoropyrimidine RNA molecule of 57 base pairs with a molecular weight of 18.5 kDa (<a class="bk_pop" href="#TCLSPIONAptDox.REF.5">5</a>). Its 2’-fluoro-modified ribose on all pyrimidines and 3’-inverted deoxythymidine cap provide significant resistance to nuclease in blood (<a class="bk_pop" href="#TCLSPIONAptDox.REF.6">6</a>). Apt has a single 5’-CG-3’ sequence in its predicted double-stranded stem region, which is a preferred binding site for the anthracycline class of anticancer drugs such as doxorubicin (Dox) (<a class="bk_pop" href="#TCLSPIONAptDox.REF.7">7</a>). Dox intercalates within the GC pair in Apt to form physical conjugate Apt(Dox) at molar ratio of 1.11:1 (dissociation constant = 600 nM) and emit fluorescence simultaneously. Because Dox possesses high efficacy against a range of neoplasms, including acute lymphoblastic and myeloblastic leukemias, malignant lymphomas, soft tissue and bone sarcomas, and breast, ovarian, prostate bladder, gastric, and bronchogenic carcinomas (<a class="bk_pop" href="#TCLSPIONAptDox.REF.8">8</a>), this complex can be used as a PSMA-specific drug carrier to deliver Dox to PCa.</p><p>Superparamagnetic iron oxide nanoparticles (SPION) consist of magnetite (Fe<sub>3</sub>O<sub>4</sub>), which has a high magnetic susceptibility to induce a significant magnetization inside a magnetic field. The resulting microscopic field gradients diphase nearby protons and cause a reduction of T<sub>2</sub> relaxation times (<a class="bk_pop" href="#TCLSPIONAptDox.REF.9">9</a>). SPION readily forms aggregates as a result of nonspecific adsorption of plasma protein in blood, and SPION is cleared rapidly from the body by functions of the reticular endothelial system (RES) such as <i>via</i> macrophages (<a class="bk_pop" href="#TCLSPIONAptDox.REF.10">10</a>). Coating the surface of SPION with a protein-repelling polymer layer such as poly(ethyleneglycol) (PEG) can prevent the absorption of plasma proteins or cells onto the surface of SPION (<a class="bk_pop" href="#TCLSPIONAptDox.REF.11">11</a>). The coating can be conducted <i>via</i> surface trialkoxysilane as an anchor part (<a class="bk_pop" href="#TCLSPIONAptDox.REF.12">12</a>). For example, poly(3-trimethoxysilyl)propyl methacrylate-<i>r</i>-PEG methyl ether methacrylate) (poly(TMSMA-<i>r</i>-PEGMA)) is a PEG-silane copolymer consisting of surface-reactive Si(OMe)<sub>3</sub> groups and protein-repelling PEG chains (<a class="bk_pop" href="#TCLSPIONAptDox.REF.11">11</a>). This coating becomes highly stabilized by simple heat treatment through condensation of hydrolyzed silane group (Si(OH)<sub>3</sub>) to form a thermally cross-linked (TCL) polymer.</p><p>TCL-SPION-A10 RNA aptamer-doxorubicin conjugate (TCL-SPION-Apt(Dox)) is a PSMA-specific agent used for magnetic resonance imaging the delivery of the anticancer drug Dox (<a class="bk_pop" href="#TCLSPIONAptDox.REF.13">13</a>). TCL-SPION-Apt(Dox) contains three components: a PSMA-specific RNA aptamer A10 (Apt) covalently attached to the core surface as a targeting molecule and drug carrier, an anthracycline class of anticancer drug Dox as chemotherapeutic agent and optical sensor, and a TCL-SPION coated with a TCL carboxylic acid-PEG-silane copolymer as a magnetic resonance contrast agent and as a carrier for Apt(Dox). The PEGylated surface prevents protein and cell adsorption, while the carboxyl groups allow for conjugation of targeting moieties such as Apt. TCL-SPION-Apt(Dox) can be used to image the drug delivery to PCas.</p></div><div id="TCLSPIONAptDox.Synthesis"><h2 id="_TCLSPIONAptDox_Synthesis_">Synthesis</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(TCL+SPION%20+%20Apt%20+%20Dox)+AND+synthesis%0D%0A" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The preparation of TCL-SPION-Apt(Dox) was conducted in several steps (<a class="bk_pop" href="#TCLSPIONAptDox.REF.11">11</a>, <a class="bk_pop" href="#TCLSPIONAptDox.REF.13">13</a>). First, <i>N</i>-acryloxysuccinimide (NAS), 3-(trimethoxysilyl)propyl methacrylate (TMSMA), and PEG-methyl ether methacrylate (PEGMA; molecular weight ~475) were mixed at a molar ratio of 1:1:0.86 (<a class="bk_pop" href="#TCLSPIONAptDox.REF.11">11</a>). After degassing with N<sub>2</sub> for 15 min, 2,2’-azo-bis-isobutyronitrile was added for 24 h at 70ºC to initiate a free radical polymerization. The produced poly(TMSMA-<i>r</i>-PEGMA-<i>r</i>-NAS) (26.795 kDa) possessed a polydispersity of 1.646. Poly(TMSMA-<i>r</i>-pPEGMA-<i>r</i>-NAS) was further hydrolyzed to convert its trimethoxysilane and <i>N</i>-hydroxysuccinimide (NHS) ester into trihydroxysilane and carboxylic acid, respectively. Second, freshly prepared magnetite (Fe<sub>3</sub>O<sub>4</sub>) was reacted with the hydrolyzed form of poly(TMSMA-<i>r</i>-PEGMA-<i>r</i>-NSA) followed by thermal cross-linking for 2 h at 80ºC. The produced TCL-SPION, with carboxyl groups as the surface functional groups (carboxyl-TCL-SPION), was then treated with <i>N</i>-(3-dimethylaminopropyl)-<i>N</i>’-ethylcarbodiimide and NHS (<a class="bk_pop" href="#TCLSPIONAptDox.REF.13">13</a>). Commercially available <i>N</i>-terminated A10 aptamer (57 base pairs) was added 15 min later and reacted for 4 h to produce TCL-SPION-Apt, in which the molar ratio of PEG, Si(OCH<sub>3</sub>)<sub>3</sub>, and NHS-activated carboxylic acid was determined with <sup>1</sup>H nuclear magnetic resonance imaging to be 1:0.85:0.71. Finally, unreacted Apt was removed and Dox was loaded to TCL-SPION-Apt to form the intercalated conjugate TCL-SPION-Apt(Dox). The molecular sizes were 60.8 ± 1.9 nm for TCL-SPION and 66.4 ± 1.5 nm for TCL-SPION-Apt.</p></div><div id="TCLSPIONAptDox.In_Vitro_Studies_Tes"><h2 id="_TCLSPIONAptDox_In_Vitro_Studies_Tes_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(TCL+%20SPION%20+%20Apt%20+%20Dox)+AND+%22in+vitro%22" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Wang et al. studied the <i>in vitro</i> cellular uptake of TCL-SPION-Apt (<a class="bk_pop" href="#TCLSPIONAptDox.REF.13">13</a>). PSMA-expressing PCa cells (LNCaP) and non-PSMA-expressing PCa cells (PC3) were incubated with 0.1 mg/ml TCL-SPION-Apt at 37ºC at time intervals of 1, 3, 6, 12, 18, and 24 h and followed by Prussian blue staining. The uptake of TCL-SPION-Apt in LNCaP cells was found as early as 3 h and gradually increased in a time-dependent manner, whereas no apparent cellular uptake was observed in PC3 cells. This result demonstrated differential targeting of PSMA-expressing PCa cells by TCL-SPION-Apt. The alteration of relaxation times (T<sub>1</sub>, T<sub>2</sub>) caused by cellular uptake of TCL-SPION-Apt was examined with nuclear magnetic resonance measurement (<a class="bk_pop" href="#TCLSPIONAptDox.REF.13">13</a>). LNCap cells and PC3 cells were incubated for 6 h with TCL-SPION-Apt. A dramatic decrease was found only in the LNCaP cells, in which T<sub>1</sub> decreased from 1,939 ± 116 to 263 ± 23 ms and T<sub>2</sub> decreased from 104 ± 1.4 to 26.6 ± 0.4 ms. As a control, LNCap cells and PC3 cells were also incubated with non-targeted TCL-SPION for 6 h. Only a small alteration was observed in the LNCaP cells in that T<sub>1</sub> decreased slightly from 1,939 ± 116 to 1,521 ± 201 ms and T<sub>2</sub> decreased 104 ± 1.4 to 89.8 ± 1.1 ms. These data exhibited a high sensitivity in detecting PSMA-expressing PCa cells. The effect of TCL-SPION-Apt(Dox) on cellular proliferation was examined <i>in vitro</i> (<a class="bk_pop" href="#TCLSPIONAptDox.REF.13">13</a>). After incubation with TCL-SPION-Apt(Dox) (0.1 mg/ml intercalated with 5 μM Dox) for 3 h, the viability was evaluated with methylthiazole tetrazolium (MTT) assay, which was 47.3 ± 1.4% for LNCaP cells and 69.3 ± 1.7% for PC3 cells. The free Dox was shown to be equipotent against both LNCaP and PC3 cell lines.</p></div><div id="TCLSPIONAptDox.Animal_Studies"><h2 id="_TCLSPIONAptDox_Animal_Studies_">Animal Studies</h2><div id="TCLSPIONAptDox.Rodents"><h3>Rodents</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(TCL+%20SPION%20+%20Apt%20+%20Dox)%20+AND++rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="TCLSPIONAptDox.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22%20SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20%28dog%20OR%20rabbit%20OR%20pig%20OR%20sheep%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="TCLSPIONAptDox.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(TCL+%20SPION%20+%20Apt%20+%20Dox)%20+AND+(primate+non+human)" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="TCLSPIONAptDox.Human_Studies"><h2 id="_TCLSPIONAptDox_Human_Studies_">Human Studies</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(TCL+%20SPION%20+%20Apt%20+%20Dox)%20+AND+human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p><div id="TCLSPIONAptDox.NIH_Support"><h3>NIH Support</h3><p>CA 119349, EB 03647</p></div></div><div id="TCLSPIONAptDox.references"><h2 id="_TCLSPIONAptDox_references_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.1">Ghosh A. , Heston W.D. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. <span><span class="ref-journal">J Cell Biochem. </span>2004;<span class="ref-vol">
|
||
<strong>91</strong>
|
||
</span>(3):528–39.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14755683" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14755683</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.2">Ng E.W. , Shima D.T. , Calias P. , Cunningham E.T. Jr, Guyer D.R. , Adamis A.P. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. <span><span class="ref-journal">Nat Rev Drug Discov. </span>2006;<span class="ref-vol">
|
||
<strong>5</strong>
|
||
</span>(2):123–32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16518379" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16518379</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.3">Levy-Nissenbaum E. , Radovic-Moreno A.F. , Wang A.Z. , Langer R. , Farokhzad O.C. Nanotechnology and aptamers: applications in drug delivery. <span><span class="ref-journal">Trends Biotechnol. </span>2008;<span class="ref-vol">
|
||
<strong>26</strong>
|
||
</span>(8):442–449.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18571753" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18571753</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.4">Hicke B.J. , Stephens A.W. Escort aptamers: a delivery service for diagnosis and therapy. <span><span class="ref-journal">J Clin Invest. </span>2000;<span class="ref-vol">
|
||
<strong>106</strong>
|
||
</span>(8):923–8.</span> [<a href="/pmc/articles/PMC314349/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC314349</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11032850" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11032850</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.5">Lupold S.E. , Hicke B.J. , Lin Y. , Coffey D.S. Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. <span><span class="ref-journal">Cancer Res. </span>2002;<span class="ref-vol">
|
||
<strong>62</strong>
|
||
</span>(14):4029–33.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12124337" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12124337</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.6">Farokhzad O.C. , Jon S. , Khademhosseini A. , Tran T.N. , Lavan D.A. , Langer R. Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer cells. <span><span class="ref-journal">Cancer Res. </span>2004;<span class="ref-vol">
|
||
<strong>64</strong>
|
||
</span>(21):7668–72.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15520166" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15520166</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.7">Zhang L. , Radovic-Moreno A.F. , Alexis F. , Gu F.X. , Basto P.A. , Bagalkot V. , Jon S. , Langer R.S. , Farokhzad O.C. Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle-aptamer bioconjugates. <span><span class="ref-journal">ChemMedChem. </span>2007;<span class="ref-vol">
|
||
<strong>2</strong>
|
||
</span>(9):1268–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17600796" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17600796</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.8">Bagalkot V. , Farokhzad O.C. , Langer R. , Jon S. An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. <span><span class="ref-journal">Angew Chem Int Ed Engl. </span>2006;<span class="ref-vol">
|
||
<strong>45</strong>
|
||
</span>(48):8149–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17099918" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17099918</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.9">Bulte J.W. , Brooks R.A. , Moskowitz B.M. , Bryant L.H. Jr, Frank J.A. T1 and T2 relaxometry of monocrystalline iron oxide nanoparticles (MION-46L): theory and experiment. <strong>Suppl 1</strong><span><span class="ref-journal">Acad Radiol. </span>1998;<span class="ref-vol">
|
||
<strong>5</strong>
|
||
</span>:S137–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9561064" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9561064</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.10">Lee H. , Lee E. K. Kim do, N.K. Jang, Y.Y. Jeong, and S. Jon, Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging. <span><span class="ref-journal">J Am Chem Soc. </span>2006;<span class="ref-vol">
|
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<strong>128</strong>
|
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</span>(22):7383–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16734494" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16734494</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.11">Lee H. , Yu M.K. , Park S. , Moon S. , Min J.J. , Jeong Y.Y. , Kang H.W. , Jon S. Thermally cross-linked superparamagnetic iron oxide nanoparticles: synthesis and application as a dual imaging probe for cancer in vivo. <span><span class="ref-journal">J Am Chem Soc. </span>2007;<span class="ref-vol">
|
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<strong>129</strong>
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||
</span>(42):12739–45.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17892287" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17892287</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.12">Jon S. , Seong J. , Khademhosseini A. , Tran T.N.T. , Laibinis P.E. , Langer R. Constructtion of Nonbiofouling surfaces by polymeric self-aassembled monolayers. <span><span class="ref-journal">Langmuir. </span>2003;<span class="ref-vol">
|
||
<strong>19</strong>
|
||
</span>(24):9989.</span></div></dd><dt>13.</dt><dd><div class="bk_ref" id="TCLSPIONAptDox.REF.13">Wang, A.Z., V. Bagalkot, C.C. Vasilliou, F. Gu, F. Alexis, L. Zhang, M. Shaikh, K. Yuet, M.J. Cima, R. Langer, P.W. Kantoff, N.H. Bander, S. Jon, and O.C. Farokhzad, Superparamagnetic Iron Oxide Nanoparticle-Aptamer Bioconjugates for Combined Prostate Cancer Imaging and Therapy. ChemMedChem, 2008. [<a href="/pmc/articles/PMC3131111/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3131111</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18613203" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18613203</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
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<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK23367</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/20641568" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">20641568</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/micad/">Contents</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/SPIO_alginate/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/PEG-S-Au-SPIO/" title="Next page in this title">Next ></a></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK23367/?report=reader">PubReader</a></li><li><a href="/books/NBK23367/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK23367" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK23367" style="display:none" title="Cite this Page"><div class="bk_tt">Zhang H. Thermally cross-linked superparamagnetic iron oxide nanoparticle-A10 RNA aptamer-doxorubicin conjugate. 2008 Aug 29 [Updated 2008 Oct 8]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK23367/pdf/Bookshelf_NBK23367.pdf">PDF version of this page</a> (135K)</li><li><a href="/books/n/micad/toc/bin/micad.csv">MICAD summary (CSV file)</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#TCLSPIONAptDox.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#TCLSPIONAptDox.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#TCLSPIONAptDox.In_Vitro_Studies_Tes" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#TCLSPIONAptDox.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#TCLSPIONAptDox.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#TCLSPIONAptDox.references" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Search MICAD</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-application" id="Shutter"></a></div><div class="portlet_content"><form xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" name="frmSearch" method="get" action="/books/NBK5330/" id="frmSearch"><script type="text/javascript" src="/corehtml/pmc//js/bookshelf/micad.js">/**/</script><label class="offscreen_noflow" for="txtfield">Search term</label><input id="txtfield" type="text" name="f1_term" size="22" onKeyPress="KeyPress('micad',event,'/books/NBK5330/','')" /><button name="f1_search" type="submit">Go</button><button onclick="this.form.reset();" type="reset">Clear</button><p><b>Limit my Search:</b></p><div class="clearfix"><label for="detection">Method of detection:</label><div class="right"><select name="detection" id="detection" style="width:200px"><option value="" selected="selected">Any</option><option value="(MRI OR "Magnetic resonance imaging" OR MRS)">MRI</option><option value="Multimodal">Multimodal imaging</option><option value="Optical">Optical imaging</option><option value="PET">PET</option><option value="Photoacoustic">Photoacoustic imaging</option><option value="(SPECT OR planar)">SPECT</option><option value="Ultrasound">Ultrasound</option><option value="(x-ray OR ct)">X-ray, CT</option></select></div></div><div class="clearfix"><label for="signal">Source of signal/contrast:</label><div class="right"><select name="signal" id="signal" style="width:200px"><option value="" selected="selected">Any</option><optgroup label="MRI agents"><option value="(Copper OR Cu)">Copper</option><option value="(Europium OR Eu3+)">Europium</option><option value="(Fluorine OR 19F)">Fluorine</option><option value="(Gadolinium OR Gd3+)">Gadolinium</option><option value=""Hyperpolarized 13C"">Hyperpolarized 13C</option><option value=""Iron oxide"">Iron oxide</option><option value=""Nitroxide radicals"">Nitroxide radicals</option><option value="(Oxygen OR 17O)">Oxygen</option><option value="Thulium">Thulium</option></optgroup><optgroup label="Multimodal agents"><option value="((Gadolinium OR Gd3+) AND Optical)">Gadolinium and optical</option><option value="((Gadolinium OR Gd3+) AND (Gold OR Au))">Gadolinium and Gold</option><option value="("Iron oxide" AND (64Cu OR 124I OR 111In))">Iron oxide and
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value="Nanobubbles">Nanobubbles</option></optgroup><optgroup label="X-ray and CT agents"><option value="(Bismuth OR Bi)">Bismuth</option><option value="(Gold OR Au)">Gold</option><option value="Iodine">Iodine</option></optgroup></select></div></div><div class="clearfix"><label for="agent">Agent Category:</label><div class="right"><select name="agent" id="agent" style="width:200px"><option value="" selected="selected">Any</option><option value="(antibody OR trastuzumab OR immunoglobulin)">Antibodies</option><option value="(bacteria OR bacteriophage OR coli)">Bacteria</option><option value="cell">Cells</option><option value="(compound OR "amino acid" OR "folic acid" OR "cage molecule" OR carbohydrate OR copolymers OR polymer OR "small molecule" OR macromolecule OR triiodobenzoate OR estradiol OR glycosaminoglycan)">Compounds</option><option value="ligand">Ligands</option><option value="(lipid OR liposome OR liposomes">Lipids</option><option value="metal">Metal</option><option value="(nanoparticle OR nanoparticles OR nanotubes OR "iron oxide")">Nanoparticles</option><option value="(siRNA OR "nucleic acid" OR oligonucleotide)">Nucleic acids</option><option value="peptide">Peptides</option><option value="polyeptide">Polyeptides</option><option value="(protein OR albumin OR chemokin OR immunoprotein OR luciferase OR albumin)">Proteins</option><option value="(virus OR adenovirus)">Viruses</option></select></div></div><div class="clearfix"><label for="target">Target Category:</label><div class="right"><select name="target" id="target" style="width:200px"><option value="" selected="selected">Any</option><option value="acceptor">Acceptors</option><option value=""adhesion molecule"">Adhesion molecules</option><option value="(antigen OR antibody-antigen)">Antigens</option><option value="(enzyme OR enzymes OR enzyme-substrate)">Enzymes</option><option value="(lipids OR lipophilic cation)">Lipids</option><option value="(receptor OR receptors OR receptor-ligand OR 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