<meta charset="utf8"></head><body>쥐 교모세포종에서 영상 유도 치료 전달을 위한 산화철 나노입자

<ol>
	<li>Tan, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Management+of+glioblastoma:+State+of+the+art+and+future+directions.">Management of glioblastoma: State of the art and future directions.</a> CA Cancer J Clin. 70 (4), 299-312 (2020).</li><li>Cihoric, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+status+and+perspectives+of+interventional+clinical+trials+for+glioblastoma+-+analysis+of+clinicaltrials.Gov.">Current status and perspectives of interventional clinical trials for glioblastoma - analysis of clinicaltrials.Gov.</a> Radiat Oncol. 12 (1), 1 (2017).</li><li>Lee, S. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temozolomide+resistance+in+glioblastoma+multiforme.">Temozolomide resistance in glioblastoma multiforme.</a> Genes Dis. 3 (3), 198-210 (2016).</li><li>Dong, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+strategies+for+brain+drug+delivery.">Current strategies for brain drug delivery.</a> Theranostics. 8 (6), 1481-1493 (2018).</li><li>Teleanu, D. M., Chircov, C., Grumezescu, A. M., Volceanov, A., Teleanu, R. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood-brain+delivery+methods+using+nanotechnology.">Blood-brain delivery methods using nanotechnology.</a> Pharmaceutics. 10 (4), 268 (2018).</li><li>Ohta, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Investigating+the+optimum+size+of+nanoparticles+for+their+delivery+into+the+brain+assisted+by+focused+ultrasound-induced+blood-brain+barrier+opening.">Investigating the optimum size of nanoparticles for their delivery into the brain assisted by focused ultrasound-induced blood-brain barrier opening.</a> Sci Rep. 10 (1), 18220 (2020).</li><li>Teplyuk, N. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Therapeutic+potential+of+targeting+microrna-10b+in+established+intracranial+glioblastoma:+First+steps+toward+the+clinic.">Therapeutic potential of targeting microrna-10b in established intracranial glioblastoma: First steps toward the clinic.</a> EMBO Mol Med. 8 (3), 268-287 (2016).</li><li>Dube, T., Kumar, N., Bishnoi, M., Panda, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual+blood-brain+barrier-glioma+targeting+peptide-poly(levodopamine)+hybrid+nanoplatforms+as+potential+near+infrared+phototheranostic+agents+in+glioblastoma.">Dual blood-brain barrier-glioma targeting peptide-poly(levodopamine) hybrid nanoplatforms as potential near infrared phototheranostic agents in glioblastoma.</a> Bioconjug Chem. 32 (9), 2014-2031 (2021).</li><li>Yoo, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+of+nanodrugs+for+mirna+targeting+in+tumor+cells.">Design of nanodrugs for mirna targeting in tumor cells.</a> J Biomed Nanotechnol. 10 (6), 1114-1122 (2014).</li><li>Medarova, Z., Pham, W., Farrar, C., Petkova, V., Moore, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+imaging+of+sirna+delivery+and+silencing+in+tumors.">In vivo imaging of sirna delivery and silencing in tumors.</a> Nature Medicine. 13 (3), 372-377 (2007).</li><li>Chen, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Co-administration+of+temozolomide+(tmz)+and+the+experimental+therapeutic+targeting+mir-10b,+profoundly+affects+the+tumorigenic+phenotype+of+human+glioblastoma+cells.">Co-administration of temozolomide (tmz) and the experimental therapeutic targeting mir-10b, profoundly affects the tumorigenic phenotype of human glioblastoma cells.</a> Front Mol Biosci. 10, 1179343 (2023).</li><li>Irtenkauf, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimization+of+glioblastoma+mouse+orthotopic+xenograft+models+for+translational+research.">Optimization of glioblastoma mouse orthotopic xenograft models for translational research.</a> Compar Med. 67 (4), 300-300 (2017).</li><li>Moore, A., Marecos, E., Bogdanov, A., Weissleder, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumoral+distribution+of+iron+oxide+nanoparticles+in+a+rodent+model.">Tumoral distribution of iron oxide nanoparticles in a rodent model.</a> Radiology. 214 (2), 568-574 (2000).</li><li>Moore, A., Medarova, Z., Potthast, A., Dai, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+targeting+of+underglycosylated+muc-1+tumor+antigen+using+a+multimodal+imaging+probe.">In vivo targeting of underglycosylated muc-1 tumor antigen using a multimodal imaging probe.</a> Cancer Res. 64 (5), 1821-1827 (2004).</li><li>Yoo, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Therapy+targeted+to+the+metastatic+niche+is+effective+in+a+model+of+stage+iv+breast+cancer.">Therapy targeted to the metastatic niche is effective in a model of stage iv breast cancer.</a> Sci Rep. 7, 45060 (2017).</li><li>Dadfar, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Iron+oxide+nanoparticles:+Diagnostic,+therapeutic+and+theranostic+applications.">Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications.</a> Adv Drug Deliv Rev. 138, 302-325 (2019).</li></ol>

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Athymic nude &#34;J:NU&#34; mice</td>
			<td>Jackson Laboratory</td>
			<td>RRID:IMSR_JAX:007850</td>
			<td>Immunocompromised mouse model</td>
		</tr>
		<tr>
			<td>0.25% Trypsin</td>
			<td>Gibco</td>
			<td>25200-056</td>
			<td>Cell culture reagent for U251</td>
		</tr>
		<tr>
			<td>1.7 mL microcentrifuge tube</td>
			<td>DOT Scientific</td>
			<td>RN1700-GMT</td>
			<td>For tissue collection</td>
		</tr>
		<tr>
			<td>10 &#181;L, Neuros Syringe, Model 1701 RN, 33 gauge, Point Style 4</td>
			<td>Hamilton</td>
			<td>65460-06</td>
			<td>Syringe for intracranial implantation of tumor cells</td>
		</tr>
		<tr>
			<td>3M Vetbond</td>
			<td>3M</td>
			<td>1469SB</td>
			<td>Tissue adhesive for surgical site closure</td>
		</tr>
		<tr>
			<td>4% Paraformaldehyde&#160;</td>
			<td>Thermo Scientific</td>
			<td>J199943-K2</td>
			<td>Tissue fixing solution</td>
		</tr>
		<tr>
			<td>70% isopropoyl alcohol wipe</td>
			<td>Cardinal</td>
			<td>MW-APL</td>
			<td>Topical antiseptic wipe for tumor implantation and tail vein injection</td>
		</tr>
		<tr>
			<td>Aperio Versa</td>
			<td>Leica</td>
			<td></td>
			<td>For scanning of stained tissue section slides</td>
		</tr>
		<tr>
			<td>Betadine Surgical Scrub</td>
			<td>Purdue</td>
			<td>6761815101</td>
			<td>Topical antiseptic for tumor implantation</td>
		</tr>
		<tr>
			<td>BioSpec 70/30</td>
			<td>Bruker</td>
			<td></td>
			<td>Magnetic resonance imaging scanner</td>
		</tr>
		<tr>
			<td>Bone Wax</td>
			<td>Medline</td>
			<td>DYNJBW25</td>
			<td>Bone wax for sealing implantation site</td>
		</tr>
		<tr>
			<td>Burrs for Micro drill</td>
			<td>F.S.T.</td>
			<td>19007-05</td>
			<td>Drill burr used to make hole in skull for tumor implantation</td>
		</tr>
		<tr>
			<td>DAPI Fluoromount-G</td>
			<td>SouthernBiotech</td>
			<td>0100-20</td>
			<td>Tissue mounting media containing DAPI stain</td>
		</tr>
		<tr>
			<td>Dulbecco&#8217;s Modified Eagle Medium (DMEM)</td>
			<td>Gibco</td>
			<td>11995-065</td>
			<td>Cell culture media for U251</td>
		</tr>
		<tr>
			<td>Extra Fine Graefe Forceps</td>
			<td>F.S.T.</td>
			<td>11150-10</td>
			<td>Sugical tool for tumor implantation</td>
		</tr>
		<tr>
			<td>Fetal bovine serum</td>
			<td>Corning</td>
			<td>35-010-CV</td>
			<td>Cell culture media supplement for U251</td>
		</tr>
		<tr>
			<td>Fine Scissors - Sharp 10.5cm</td>
			<td>F.S.T.</td>
			<td>14060-10</td>
			<td>Sugical tool for tumor implantation</td>
		</tr>
		<tr>
			<td>Glydo (Lidocaine)</td>
			<td>Sagent</td>
			<td>673-76</td>
			<td>Topical analgesic for surgical site</td>
		</tr>
		<tr>
			<td>Ideal Micro Drill</td>
			<td>CellPoint Scientific</td>
			<td>67-1200A</td>
			<td>Drill used to make hole in skull for tumor implantation</td>
		</tr>
		<tr>
			<td>Insulin syringe 1CC 29G X 1/2&#34;</td>
			<td>Becton, Dickinson</td>
			<td>324704</td>
			<td>Syringe for D-Luciferin injection and tail vein injection of nanoparticles</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Covetrus</td>
			<td>11695067772</td>
			<td>Anethesia</td>
		</tr>
		<tr>
			<td>Isoflurane vaporizer</td>
			<td>SOMNI Scientific</td>
			<td>VS6002</td>
			<td>Anethesia apparatus</td>
		</tr>
		<tr>
			<td>IVIS SpectrumCT In Vivo Imaging System</td>
			<td>PerkinElmer/Revvity</td>
			<td>128201</td>
			<td>Bioluminescence and fluorescence imaging scanner</td>
		</tr>
		<tr>
			<td>IVISbrite D-Luciferin Potassium Salt</td>
			<td>PerkinElmer/Revvity</td>
			<td>122799-100MG</td>
			<td>Substrate for bioluminescence imaging</td>
		</tr>
		<tr>
			<td>Ketaset (Ketamine)</td>
			<td>Zoetis</td>
			<td>10004027</td>
			<td>Anesthetic for tumor implantation surgery</td>
		</tr>
		<tr>
			<td>Ketofen (Ketoprofen)</td>
			<td>Zoetis</td>
			<td>10004031</td>
			<td>Analgesic for tumor implantation surgery</td>
		</tr>
		<tr>
			<td>Leica CM1950</td>
			<td>Leica</td>
			<td>CM1950</td>
			<td>For cryosectioning of OCT-embedded samples</td>
		</tr>
		<tr>
			<td>PBS</td>
			<td>Gibco</td>
			<td>14190-144</td>
			<td>Cell culture reagent and cell suspension solution for implantation of U251</td>
		</tr>
		<tr>
			<td>Penicillin-streptomycin</td>
			<td>Gibco</td>
			<td>15140-122</td>
			<td>Antibiotic for cell culture media for U251</td>
		</tr>
		<tr>
			<td>Puralube vet ointment</td>
			<td>MWI Veterinary</td>
			<td>27505</td>
			<td>Opthalmic eye ointment for protection during tumor implantation</td>
		</tr>
		<tr>
			<td>Ruler</td>
			<td>F.S.T.</td>
			<td>18000-30</td>
			<td>Used to measure drill site for implanation</td>
		</tr>
		<tr>
			<td>Tissue-Tek Cryomold&#160; Intermediate 15 x 15 x 5 mm</td>
			<td>Sakura</td>
			<td>4566</td>
			<td>Collection mold for collecting tissue samples</td>
		</tr>
		<tr>
			<td>Tissue-Tek&#160;O.C.T. Compound</td>
			<td>Sakura</td>
			<td>4583</td>
			<td>Freezing compound for collecting tissue samples</td>
		</tr>
		<tr>
			<td>U-251 MG cell line human</td>
			<td>Millapore Sigma</td>
			<td>9063001</td>
			<td>Human glioblastoma cell line</td>
		</tr>
		<tr>
			<td>Xylazine Injectable Solution, 100 mg/ml</td>
			<td>Covetrus</td>
			<td>1XYL006</td>
			<td>Paralytic for tumor implantation surgery</td>
		</tr>
	</tbody>
</table>

nanoparticle delivery of an oligonucleotide payload in a glioblastoma multiforme animal model

Glioblastoma multiforme (GBM) is the highest grade of astrocytoma for which there is virtually no cure. Approximately 15,000 people are diagnosed with glioblastoma annually, which has a dismal median survival of about 15 months and a 5-year survival rate of 5%1. In the past decades, there has been marginal improvement in prognosis despite multiple efforts to advance therapeutic options. The current standard of care for GBM includes maximal surgical resection, when feasible, followed by radiotherapy and chemotherapy2. Temozolomide (TMZ), the chemotherapy of choice, was the latest therapy for glioblastoma discovered to show notable clinical efficacy; however, at least 50% of GBM tumors show TMZ resistance3. In spite of this rigorous therapeutic regimen, there is still a significant clinical need for improved glioblastoma therapy.
The development of therapeutics for GBM and other brain-related diseases is significantly hampered by the selective nature of the blood-brain barrier (BBB). The BBB is a physiological barrier comprised of endothelial cells, pericytes, and astrocyte feet-ends, which creates the semi-permeable membrane between the circulatory system and the brain, restricting the free passage of molecules and cells into the brain4. While protective in normal physiology and critical for brain homeostasis, the BBB prevents many therapeutics from reaching the brain, complicating the treatment of GBM. Efforts to enhance the delivery of therapeutics to GBM have led to the development of nanoparticle-based delivery vehicles, focused ultrasound drug delivery enhancement, and receptor-mediated drug delivery5,6.
Nanoparticles have emerged as a promising medium for developing therapeutics for a myriad of diseases, including cancers. The application of nanoparticles for imaging and therapeutic purposes in GBM has been attempted using various nanoparticle constructs7,8. With the focus on delivering drugs to GBM in conjunction with in vivo imaging of the delivery, the proposed approach utilizes magnetic nanoparticles (MN) consisting of an iron oxide core and covered by dextran for stability. The magnetic properties of these nanoparticles afford for their detection by magnetic resonance (MR) imaging, while simple conjugation chemistry to the aminated dextran coating allows for conjugation of therapeutic moieties such as RNA molecules, additional targeting moieties, or imaging moieties (such as Cy5.5 near-infrared optical dye)9,10. In addition to the imaging capabilities, the nano platform is able to extend the half-life of RNA therapeutics by protecting the oligonucleotide from endogenous nucleases, improving therapeutic delivery. Here, the application of this nano platform for in vivo delivery of therapeutic oligonucleotides (termed MN-anti-miR10b) to GBM, monitored by in vivo imaging, is presented. Previously, the ability of this nano platform to accumulate was demonstrated in GBM cells in vitro, causing significant loss of viability of tumor cells11. Prior to performing therapeutic in vivo studies, it is necessary to demonstrate in vivo delivery of this nano platform to GBM tumors in animal models. To achieve this, orthotopic GBM animal models were produced, and intravenous administration of the construct was performed followed by in vivo imaging. Outlined here are the protocols of these studies showing accumulation in the tumor region confirmed by in vivo imaging and ex vivo microscopy.

<meta charset="utf8"></head><body>저자 스포트라이트: 교모세포종 치료를 위한 산화철 나노입자를 사용한 혁신적인 암 치료법

Glioblastoma multiforme animal model에서 oligonucleotide payload의 나노입자 전달

Our research focuses on the development of cancer therapies using our iron oxide nanoparticle delivery platform. The advantage of our nanoplatform is its ability to cross the blood brain barrier and accumulate in the tumor, delivering therapeutics. The goal is to add to the small arsenal of available therapies for glioblastoma.The blood-brain barrier presents a challenge for the delivery of therapeutics to glioblastoma. Many compounds are unable to cross the barrier, making systemic administration of drugs for glioblastoma treatment near impossible. Currently available systemic treatments for this disease have many off target toxicities.Our nanoplatform overcomes this limitation by helping therapeutic moieties traverse the blood-brain barrier. The delivery of the therapeutic oligonucleotide to the tumor site can be monitored by various imaging modalities, making it a clinically relevant tool. The modular nature of the nanoplatform allows for tailor-made therapies to be developed, offering flexibility to address the vast molecular heterogeneity in glioblastoma subtypes.This precision medicine approach with superior blood-brain barrier penetrance, allows us to expand upon limited therapeutic options.

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain malignancy for which there is no cure. The blood-brain barrier is a ...

nanoparticle-delivery-an-oligonucleotide-payload-glioblastoma

Without Section

Research

Nanoparticle Delivery of an Oligonucleotide Payload in a Glioblastoma Multiforme Animal Model

JoVE Journal

Cancer Research

778 조회수.  Michigan State University. 우리의 연구는 산화철 나노입자 전달 플랫폼을 사용한 암 치료법 개발에 중점을 둡니다. 당사의 나노플랫폼의 장점은 혈액뇌장벽을 통과하여 종양에 축적되어 치료제를 전달하는 능력입니다. 목표는 교모세포종에 대한 사용 가능한 치료법의 작은 무기고에 추가하는 것입니다.혈액-뇌 장벽은 교모세포종에 대한 치료제 전달에 어려움을 제기합...