This research is funded by an operating grant from the Canadian Institutes of Health Research (CIHR) to C.A. and D.A.J. The authors acknowledge the Canadian Foundation for Innovation and Princess Margaret Cancer Foundation for funding the STTARR research facility that enables the imaging and therapy research components of this work.

<ol>
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D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Hyperthermia in cancer treatment: a primer. , (2006).</li><li>Landon, C. D., Park, J. Y., Needham, D., Dewhirst, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanoscale+Drug+Delivery+and+Hyperthermia:+The+Materials+Design+and+Preclinical+and+Clinical+Testing+of+Low+Temperature-Sensitive+Liposomes+Used+in+Combination+with+Mild+Hyperthermia+in+the+Treatment+of+Local+Cancer.">Nanoscale Drug Delivery and Hyperthermia: The Materials Design and Preclinical and Clinical Testing of Low Temperature-Sensitive Liposomes Used in Combination with Mild Hyperthermia in the Treatment of Local Cancer.</a> Open Nanomed. 3, 38-64 (2011).</li><li>Koning, G. A., Eggermont, A. M., Lindner, L. H., ten Hagen, T. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperthermia+and+thermosensitive+liposomes+for+improved+delivery+of+chemotherapeutic+drugs+to+solid+tumors.">Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors.</a> Pharm Res. 27 (8), 1750-1754 (2010).</li><li>Viglianti, B. L., 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=In+vivo+monitoring+of+tissue+pharmacokinetics+of+liposome/drug+using+MRI:+illustration+of+targeted+delivery.">In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: illustration of targeted delivery.</a> Magn Reson Me. 51 (6), 1153-1162 (2004).</li><li>Ponce, A. 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=Magnetic+resonance+imaging+of+temperature-sensitive+liposome+release:+drug+dose+painting+and+antitumor+effects.">Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects.</a> J Natl Cancer Ins. 99 (1), 53-63 (2007).</li><li>Kong, G., 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=Efficacy+of+liposomes+and+hyperthermia+in+a+human+tumor+xenograft+model:+importance+of+triggered+drug+release.">Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release.</a> Cancer Res. 60 (24), 6950-6957 (2000).</li><li>Yarmolenko, P. 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=Comparative+effects+of+thermosensitive+doxorubicin-containing+liposomes+and+hyperthermia+in+human+and+murine+tumours.">Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours.</a> Int J Hyperthermia. 26 (5), 485-498 (2010).</li><li>Wang, L. H., Jacques, S. L., Zheng, L. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MCML-Monte+Carlo+modeling+of+photon+transport+in+multi-layered+tissues.">MCML-Monte Carlo modeling of photon transport in multi-layered tissues.</a> Comput Meth Prog Bio. 47, 131-146 (1995).</li><li>Rieke, V., Butts Pauly, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+thermometry.">MR thermometry.</a> J Magn Reson Imaging. 27 (2), 376-390 (2008).</li><li>Dou, Y. 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=Heat-activated+thermosensitive+liposomal+cisplatin+(HTLC)+results+in+effective+growth+delay+of+cervical+carcinoma+in+mice.">Heat-activated thermosensitive liposomal cisplatin (HTLC) results in effective growth delay of cervical carcinoma in mice.</a> J Control Release. 178, 69-78 (2014).</li><li>Lammers, T., Kiessling, F., Hennink, W. E., Storm, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanotheranostics+and+image-guided+drug+delivery:+current+concepts+and+future+directions.">Nanotheranostics and image-guided drug delivery: current concepts and future directions.</a> Mol Pharm. 7 (6), 1899-1912 (2010).</li><li>Lee, H., 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=A+novel+64Cu-liposomal+PET+agent+(MM-DX-929)+predicts+response+to+liposomal+chemotherapeutics+in+preclinical+breast+cancer+models.">A novel 64Cu-liposomal PET agent (MM-DX-929) predicts response to liposomal chemotherapeutics in preclinical breast cancer models.</a> Thirty-Fifth Annual CTRC-AACR San Antonio Breast Cancer Symposium. , (2012).</li></ol>

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تم تطوير الجسيمات الشحمية لأول مرة في 1960s بوصفها وسائل إيصال المخدرات التي تحمل المخدرات ماء في حجم مائي داخلي والعقاقير مسعور داخل دهن طبقة ثنائية. 2. بالإضافة إلى استخدام في التطبيقات العلاجية، تم استكشاف الجسيمات الشحمية لتطبيقات التشخيص عند المسمى مع النوي...

الفيزيولوجيا المرضية النتائج الأورام الصلبة في نفاذية تعزيز والاستبقاء (EPR) نظم النانو. وقد أدى ذلك إلى تطوير العديد من نظم لتقديم الأدوية التي تستفيد من هذا التأثير لاستهداف الأنسجة السرطانية مع تقليل الآثار الجانبية الجهازية 1. تم التحقيق فيها على نطاق واسع تسليم التكنولوجيات Liposomal للتحقيقات المخدرات أو التصوير 2. على الرغم من الجسيمات الشحمية ساهمت كثيرا في تقليل سمية جهازية بالمقارنة مع العلاج الكيميائي التقليدي، كانت هناك بعض التحسينات في السريرية فعالية 3،4. وقد أظهرت الدراسات أن هي فعالية محدودة بسبب عدم وجود الافراج المخدرات من الناقل 4،5. ونتيجة لذلك، وقد اجتذب تطوير الجسيمات الشحمية التي يتم تفعيلها للافراج عن المخدرات مغلفة في الاستجابة للمؤثرات الخارجية اهتماما كبيرا. وقد استخدمت ارتفاع الحرارة على مدى عقود كطريقة علاج آمن نسبيا لمرضى السرطان 6. وبالتالي فإن تطويروكانت منة من الجسيمات الشحمية للحرارة مع حرارة بمثابة الزناد الخارجي مزيج منطقي مع إمكانية كبيرة لترجمة السريرية. في الواقع، قد وصل إلى صياغة المحتوية على lysolipid للحرارة الحويصلية من دوكسوروبيسين، والمعروفة باسم LTSL-DOX، والآن التقييم السريري 7. البيانات السريرية الأخيرة مع LTSL-DOX أظهرت أن البروتوكول للتسليم الحرارة عاملا حاسما التي يمكن أن تؤثر بشكل كبير على نتائج المرضى 8. في البشر، وتستخدم الترددات الراديوية والموجات الدقيقة والليزر والموجات فوق الصوتية محولات لتطبيق ارتفاع الحرارة محليا في مواقع ورم 9. في الدراسات قبل السريرية التي تتطلب تسخين الأورام تحت الجلد، وغالبا ما تستخدم القسطرة التدفئة 10،11 وحمامات المياه 12،13. في هذه المخطوطة، ونحن نقدم طريقة جديدة لتسخين الأورام تحت الجلد باستخدام مصمم خصيصا القائم على الليزر الإعداد التدفئة، والتي تمكن قدرا أكبر من التدفئة امتثالي من حجم الورم. باستخدام MR أماه متوافقاستنباط مواد، والإعداد صغيرة بما يكفي لتناسب داخل تجويف صغير تصوير MR الحيوان، مما يسمح في الوقت الحقيقي رصد التغيرات في درجة حرارة الأنسجة أثناء التسخين ليزر. وكيل MR النقيض من ذلك، gadoteridol (ش ج-HP-DO3A)، وشارك مغلفة مع CDDP إلى صياغة الحويصلية للحرارة من CDDP (HTLC)، والمعروفة باسم ش ج-HTLC، في الوقت الحقيقي MR الرصد والتقييم للحرارة صورة الموجهة -activated الافراج عن المخدرات والمصادقة على بروتوكول التدفئة. تظهر نتائجنا أن جهاز التدفئة المعتمدة على الليزر تفعيلها بكفاءة الافراج عن وكلاء مغلفة من صياغة ش ج-HTLC في حين يجري رصدها من خلال التصوير بالرنين المغناطيسي.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Rotary evaporator</td>
			<td>Heidolph Instruments GmbH &#38; Co.KG</td>
			<td>Laborota 4000</td>
			<td></td>
		</tr>
		<tr>
			<td>High pressure extruder</td>
			<td>Northern Lipids Inc.</td>
			<td>T.001</td>
			<td>10 mL thermobarrel</td>
		</tr>
		<tr>
			<td>Heating circulator</td>
			<td>VWR International LLC.</td>
			<td>11305</td>
			<td>Connected to extruder</td>
		</tr>
		<tr>
			<td>Polycarbonate membrane filter</td>
			<td>Whatman</td>
			<td>110605;110606</td>
			<td></td>
		</tr>
		<tr>
			<td>Differential scanning calorimeter (DSC)</td>
			<td>TA Instruments</td>
			<td>Q100</td>
			<td></td>
		</tr>
		<tr>
			<td>Inductively coupled plasma-atomic emission spectrometer (ICP-AES)</td>
			<td>PerkinElmer</td>
			<td>Optima 7300DV</td>
			<td></td>
		</tr>
		<tr>
			<td>Zetasizer</td>
			<td>Malvern Instruments Ltd.</td>
			<td>Nano-ZS</td>
			<td></td>
		</tr>
		<tr>
			<td>Cell incubator</td>
			<td>NuAire Inc.</td>
			<td>NU-5800</td>
			<td></td>
		</tr>
		<tr>
			<td>Autoclip wound clip applier</td>
			<td>Becton Dickinson</td>
			<td>427630</td>
			<td></td>
		</tr>
		<tr>
			<td>Autoclip wound clip remover</td>
			<td>Becton Dickinson</td>
			<td>427637</td>
			<td></td>
		</tr>
		<tr>
			<td>Wound clips</td>
			<td>Becton Dickinson</td>
			<td>427631</td>
			<td>9 mm</td>
		</tr>
		<tr>
			<td>763 nm Laser device</td>
			<td>Biolitec</td>
			<td>Ceralas CD 403 laser</td>
			<td></td>
		</tr>
		<tr>
			<td>Laser probe</td>
			<td>Thorlabs Inc.</td>
			<td>FT400EMT</td>
			<td>With SMA and flat cleave connectors</td>
		</tr>
		<tr>
			<td>Spectralon (illuminator)</td>
			<td>Labsphere Inc.</td>
			<td>FAST-SL-5CMX5CM</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td>CSTM-SL-5CMX5CM</td>
			<td></td>
		</tr>
		<tr>
			<td>7 Tesla prelinical magnetic resonance (MR) imaging system</td>
			<td>Bruker Corporation</td>
			<td>Biospec 70/30</td>
			<td></td>
		</tr>
		<tr>
			<td>Fiber optic temperature sensor</td>
			<td>LumaSense Technologies Inc.</td>
			<td>Luxtron FOT Lab Kit</td>
			<td></td>
		</tr>
		<tr>
			<td>Integrating sphere</td>
			<td>Newport Corporation</td>
			<td>819C</td>
			<td></td>
		</tr>
		<tr>
			<td>Optical power meter</td>
			<td>Newport Corporation</td>
			<td>1830-R</td>
			<td></td>
		</tr>
	</tbody>
</table>

custom-designed laser-based heating apparatus for triggered release of cisplatin from thermosensitive liposomes with magnetic resonance image guidance

وقد استخدمت الجسيمات الشحمية كما نظم تسليم المخدرات لاستهداف الأورام الصلبة من خلال استغلال نفاذية تعزيز والاستبقاء (EPR) تأثير يؤدي إلى تخفيضات كبيرة في السمية الجهازية. ومع ذلك، وإطلاق سراح كافية من المخدرات مغلفة من الجسيمات الشحمية ومحدودة النجاعة السريرية. وقد تم تصميم الجسيمات الشحمية حساسة للحرارة لتوفير الإفراج موقع معين من المخدرات من أجل التغلب على مشكلة ورم محدود التوافر البيولوجي المخدرات. وقد صممت لدينا مختبر ووضع صياغة تنشيط حرارة حساس للحرارة الحويصلية من سيسبلاتين (CDDP)، والمعروفة باسم HTLC، لتوفير الإفراج المشغلة للCDDP في الأورام الصلبة. وقد تحقق التسليم تفعيلها الحرارة في الجسم الحي في نماذج الفئران باستخدام القائم على الليزر جهاز التدفئة مبنية خصيصا الذي يوفر نمط التدفئة امتثالي في موقع الورم وهو ما أكدته MR قياس الحرارة (MRT). تم استخدام جهاز مراقبة درجة الحرارة الألياف الضوئية لقياس درجة الحرارة في الوقت الحقيقيخلال فترة التسخين كامل مع تعديل على الانترنت التسليم الحرارة بالتناوب قوة الليزر. تم تحسين تسليم المخدرات تحت بالرنين المغناطيسي (MR) التوجيه الصورة عن طريق التعاون التغليف وكيل النقيض MR (أي gadoteridol) جنبا إلى جنب مع CDDP في الجسيمات الشحمية للحرارة كوسيلة للتحقق من صحة بروتوكول التدفئة وتقييم تراكم الورم. يتألف البروتوكول تسخين فترة التسخين لمدة 5 دقائق قبل إدارة HTLC و 20 دقيقة التدفئة بعد الحقن. أدى هذا البروتوكول التدفئة في الإفراج الفعلي من وكلاء مغلفة مع أعلى تغيير إشارة MR وحظ في الورم ساخنة بالمقارنة مع ورم القارسة والعضلات. وأظهرت هذه الدراسة أن التطبيق الناجح لجهاز التدفئة المعتمدة على الليزر لتطوير الحويصلية قبل السريرية للحرارة وأهمية التحقق من صحة MR الموجهة للبروتوكول التدفئة لتعظيم الاستفادة من تسليم المخدرات.

يتم تصنيع الجسيمات الشحمية HTLC باستخدام الطرق الشائعة، بما في ذلك تشكيل الفيلم الدهون، الماء، وقذف وغسيل الكلى. خلال الخطوات التي تنطوي CDDP، ينبغي اتخاذ الحذر بعدم تعريض CDDP إلى أي مادة الألومنيوم، كما سيتم إلغاء CDDP من خلال تشكيل وديعة الأسود. ويرد مثال على HTLC في ال...

Watch this Scientific Journal Video about Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance at JoVE

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

وقد وضعت AN-مصمم خصيصا القائم على الليزر جهاز التدفئة MRI متوافق مع توفير التدفئة المحلية الأورام تحت الجلد من أجل تفعيل الافراج عن وكلاء من الجسيمات الشحمية للحرارة على وجه التحديد في منطقة الورم.

مصمم خصيصا القائم على الليزر التدفئة جهاز لإطلاق الحفز من سيسبلاتين من حساس للحرارة الليبوزومات مع الرنين المغناطيسي الإرشاد صورة

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

custom-designed-laser-based-heating-apparatus-for-triggered-release

Research

JoVE Journal

Bioengineering

9.0K Views.  University of Toronto.  وقد وضعت AN-مصمم خصيصا القائم على الليزر جهاز التدفئة MRI متوافق مع توفير التدفئة المحلية الأورام تحت الجلد من أجل تفعيل الافراج عن وكلاء من الجسيمات الشحمية للحرارة على وجه التحديد في منطقة الورم. 

Video: Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Magnetic Resonance Elastography Methodology for the Evaluation of Tissue Engineered Construct Growth

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use of destructive assessment is not acceptable. A proposed alternative is the use of an imaging process called magnetic resonance elastography. Elastography is a nondestructive method for determining the engineered outcome by measuring local mechanical property values (i.e., complex shear modulus), which are essential markers for identifying the structure and functionality of a tissue. As a noninvasive means for evaluation, the monitoring of engineered constructs with imaging modalities such as magnetic resonance imaging (MRI) has seen increasing interest in the past decade1. For example, the magnetic resonance (MR) techniques of diffusion and relaxometry have been able to characterize the changes in chemical and physical properties during engineered tissue development2. The method proposed in the following protocol uses microscopic magnetic resonance elastography (&mu;MRE) as a noninvasive MR based technique for measuring the mechanical properties of small soft tissues3. MRE is achieved by coupling a sonic mechanical actuator with the tissue of interest and recording the shear wave propagation with an MR scanner4. Recently, &mu;MRE has been applied in tissue engineering to acquire essential growth information that is traditionally measured using destructive mechanical macroscopic techniques5. In the following procedure, elastography is achieved through the imaging of engineered constructs with a modified Hahn spin-echo sequence coupled with a mechanical actuator. As shown in Figure 1, the modified sequence synchronizes image acquisition with the transmission of external shear waves; subsequently, the motion is sensitized through the use of oscillating bipolar pairs. Following collection of images with positive and negative motion sensitization, complex division of the data produce a shear wave image. Then, the image is assessed using an inversion algorithm to generate a shear stiffness map6. The resulting measurements at each voxel have been shown to strongly correlate (R2&gt;0.9914) with data collected using dynamic mechanical analysis7. In this study, elastography is integrated into the tissue development process for monitoring human mesenchymal stem cell (hMSC) differentiation into adipogenic and osteogenic constructs as shown in Figure 2.

The procedure demonstrates the methodology of magnetic resonance elastography for monitoring the engineered outcome of adipose and osteogenic tissue engineered constructs through noninvasive local assessment of the mechanical properties using microscopic magnetic resonance elastography (&mu;MRE).

المغناطيسي منهجية Elastography الرنين لتقييم الأنسجة المهندسة النمو كونستركت

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use ...

Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging

X-ray fluoroscopy-guided endovascular procedures have several significant limitations, including difficult catheter navigation and use of ionizing radiation, which can potentially be overcome using a magnetically steerable catheter under MR guidance.
	The main goal of this work is to develop a microcatheter whose tip can be remotely controlled using the magnetic field of the MR scanner. This protocol aims to describe the procedures for applying current to the microcoil-tipped microcatheter to produce consistent and controllable deflections.
	A microcoil was fabricated using laser lathe lithography onto a polyimide-tipped endovascular catheter. In vitro testing was performed in a waterbath and vessel phantom under the guidance of a 1.5-T MR system using steady-state free precession (SSFP) sequencing. Various amounts of current were applied to the coils of the microcatheter to produce measureable tip deflections and navigate in vascular phantoms.
	The development of this device provides a platform for future testing and opportunity to revolutionize the endovascular interventional MRI environment.

Current applied to an endovascular microcatheter with microcoil tip made by laser lathe lithography can achieve controllable deflections under magnetic resonance (MR) guidance, which may improve speed and efficacy of navigation of vasculature during various endovascular procedures.

مغناطيسيا بمساعدة البعيد تلميح Microcatheter الشواهد الانحراف تحت التصوير بالرنين المغناطيسي

X-ray fluoroscopy-guided  endovascular procedures have several significant limitations, including  difficult catheter navigation and use of ionizing ...

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of smart soft devices for biomedical applications. Although a number of magnetically-responsive drug delivery systems have demonstrated efficacies through either in vitro proof of concept studies or in vivo preclinical applications, their use in clinical settings is still limited by their insufficient biocompatibility or biodegradability. Additionally, many of the existing platforms rely on sophisticated techniques for their fabrications. We recently demonstrated the fabrication of biodegradable, gelatin-based thermo-responsive microgel by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within a three-dimensional gelatin network. In this study, we present a facile method to fabricate a biodegradable drug release platform that enables a magneto-thermally triggered drug release. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and thermo-responsive polymers within gelatin-based colloidal microgels, in conjunction with an alternating magnetic field application system.

We present a facile method to fabricate a biodegradable gelatin-based drug release platform that is magneto-thermally responsive. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and poly(N-isopropylacrylamide-co-acrylamide) within a spherical gelatin micro-network crosslinked by genipin, in conjunction with an alternating magnetic field application system.

بالتناوب المغناطيسي Microgels الجيلاتين الهجين-الميدان الاستجابة لرقابة الإصدار المخدرات

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of ...

Rapid Scan Electron Paramagnetic Resonance Opens New Avenues for Imaging Physiologically Important Parameters In Vivo

We demonstrate a superior method of 2D spectral-spatial imaging of stable radical reporter molecules at 250 MHz using rapid-scan electron-paramagnetic-resonance (RS-EPR), which can provide quantitative information under in vivo conditions on oxygen concentration, pH, redox status and concentration of signaling molecules (i.e., OH&#8226;, NO&#8226;). The RS-EPR technique has a higher sensitivity, improved spatial resolution (1 mm), and shorter acquisition time in comparison to the standard continuous wave (CW) technique. A variety of phantom configurations have been tested, with spatial resolution varying from 1 to 6 mm, and spectral width of the reporter molecules ranging from 16 &#181;T (160 mG) to 5 mT (50 G). A cross-loop bimodal resonator decouples excitation and detection, reducing the noise, while the rapid scan effect allows more power to be input to the spin system before saturation, increasing the EPR signal. This leads to a substantially higher signal-to-noise ratio than in conventional CW EPR experiments.

Rapid Scan Electron Paramagnetic Resonance Opens New Avenues for Imaging Physiologically Important Parameters In Vivo

A new electron paramagnetic resonance (EPR) method, rapid scan EPR (RS-EPR), is demonstrated for 2D spectral spatial imaging which is superior to the traditional continuous wave (CW) technique and opens new venues for in vivo imaging. Results are demonstrated at 250 MHz, but the technique is applicable at any frequency.

سرعة المسح الضوئي الكترون ممغطس الرنين تفتح آفاقا جديدة للالتصوير الناحية الفسيولوجية معلمات هام<em&gt; في فيفو</em

We demonstrate a superior method of 2D spectral-spatial imaging of stable radical reporter molecules at 250 MHz using rapid-scan ...

Image-guided, Laser-based Fabrication of Vascular-derived Microfluidic Networks

This detailed protocol outlines the implementation of image-guided, laser-based hydrogel degradation for the fabrication of vascular-derived microfluidic networks embedded in PEGDA hydrogels. Here, we describe the creation of virtual masks that allow for image-guided laser control; the photopolymerization of a micromolded PEGDA hydrogel, suitable for microfluidic network fabrication and pressure head-driven flow; the setup and use of a commercially available laser scanning confocal microscope paired with a femtosecond pulsed Ti:S laser to induce hydrogel degradation; and the imaging of fabricated microfluidic networks using fluorescent species and confocal microscopy. Much of the protocol is focused on the proper setup and implementation of the microscope software and microscope macro, as these are crucial steps in using a commercial microscope for microfluidic fabrication purposes that contain a number of intricacies. The image-guided component of this technique allows for the implementation of 3D image stacks or user-generated 3D models, thereby allowing for creative microfluidic design and for the fabrication of complex microfluidic systems of virtually any configuration. With an expected impact in tissue engineering, the methods outlined in this protocol could aid in the fabrication of advanced biomimetic microtissue constructs for organ- and human-on-a-chip devices. By mimicking the complex architecture, tortuosity, size, and density of in vivo vasculature, essential biological transport processes can be replicated in these constructs, leading to more accurate in vitro modeling of drug pharmacokinetics and disease.

This protocol outlines the implementation of image-guided, laser-based hydrogel degradation to fabricate vascular-derived, biomimetic microfluidic networks embedded in poly(ethylene glycol) diacrylate (PEGDA) hydrogels. These biomimetic microfluidic systems may be useful for tissue engineering applications, generation of in vitro disease models, and fabrication of advanced "on-a-chip" devices.

صورة موجهة، التصنيع القائم على الليزر من شبكات ميكروفلويديك المستمدة الأوعية الدموية.

This detailed protocol outlines the implementation of image-guided, laser-based hydrogel degradation for the fabrication of vascular-derived microfluidic ...

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant &#34;burst release&#34; of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.

Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release

This manuscript describes the preparation of magnetic and thermal-sensitive microgels via a temperature-induced emulsion without chemical reaction. These sensitive microgels were synthesized by mixing poly(N-isopropylacrylamide) (PNIPAAm), polyethylenimine (PEI) and Fe3O4-NH2 nanoparticles for the potential use in magnetically and thermally triggered drug-release.

المغناطيسي الحساسة والحرارية بولي (<em&gt; N</em&gt; -isopropylacrylamide) ميكروجيلز المستندة إلى مغناطيسيا تسيطر عليها الإصدار

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...

Metabolic Support of Excised, Living Brain Tissues During Magnetic Resonance Microscopy Acquisition

This protocol describes the procedures necessary to support normal metabolic functions of acute brain slice preparations during the collection of magnetic resonance (MR) microscopy data. While it is possible to perform MR collections on living, excised mammalian tissue, such experiments have traditionally been constrained by resolution limits and are thus incapable of visualizing tissue microstructure. Conversely, MR protocols that did achieve microscopic image resolution required the use of fixed samples to accommodate the need for static, unchanging conditions over lengthy scan times. The current protocol describes the first available MR technique that enables imaging of living, mammalian tissue samples at microscopic resolutions. Such data is of great importance to the understanding of how pathology-based contrast changes occurring at the microscopic level influence the content of macroscopic MR scans such as those used in the clinic. Once such an understanding is realized, diagnostic methods with greater sensitivity and accuracy can be developed, which will translate directly to earlier disease treatment, more accurate therapy monitoring and improved patient outcomes.
While the described methodology focuses on brain slice preparations, the protocol is adaptable to any excised tissue slice given that changes are made to the gas and perfusate preparations to accommodate the tissue&#39;s specific metabolic needs. Successful execution of the protocol should result in living, acute slice preparations that exhibit MR diffusion signal stability for periods up to 15.5 h. The primary advantages of the current system over other MR compatible perfusion apparatuses are its compatibility with the MR microscopy hardware required to attain higher resolution images and ability to provide constant, uninterrupted flow with carefully regulated perfusate conditions. Reduced sample throughput is a consideration with this design as only one tissue slice may be imaged at a time.

The current protocol describes a method by which users can maintain viability of acute hippocampal and cortical slice preparations during the collection of magnetic resonance microscopy data.

دعم الأيضية اقتطعت، أنسجة المخ الحية أثناء الرنين المغناطيسي المجهري اقتناء

This protocol describes the procedures necessary to support normal metabolic functions of acute brain slice preparations during the collection of magnetic ...

Preparation, Purification, and Use of Fatty Acid-containing Liposomes

Liposomes containing single-chain amphiphiles, particularly fatty acids, exhibit distinct properties compared to those containing diacylphospholipids due to the unique chemical properties of these amphiphiles. In particular, fatty acid liposomes enhance dynamic character, due to the relatively high solubility of single-chain amphiphiles. Similarly, liposomes containing free fatty acids are more sensitive to salt and divalent cations, due to the strong interactions between the carboxylic acid head groups and metal ions. Here we illustrate techniques for preparation, purification, and use of liposomes comprised in part or whole of single chain amphiphiles (e.g., oleic acids).

Liposomes containing single-chain amphiphiles, particularly fatty acids, exhibit distinct properties compared to those containing diacylphospholipids due to the unique chemical properties of single chain amphiphiles. Here we describe techniques for the preparation, purification, and use of liposomes comprised in part or whole of these amphiphiles.

إعداد وتنقية، واستخدام الدهنية المحتوية على الأحماض الدهنية

Liposomes containing single-chain amphiphiles, particularly fatty acids, exhibit distinct properties compared to those containing diacylphospholipids due ...

Apparatus for Harvesting Tissue Microcolumns

This manuscript describes the production process for a laboratory apparatus, made from off-the-shelf components, that can be used to collect microcolumns of full-thickness skin tissue. The small size of the microcolumns allows donor sites to heal quickly without causing donor site scarring, while harvesting full-thickness tissue enables the incorporation of all cellular and extracellular components of skin tissue, including those associated with deeper dermal regions and the adnexal skin structures, which have yet to be successfully reproduced using conventional tissue engineering techniques. The microcolumns can be applied directly into skin wounds to augment healing, or they can be used as the autologous cell/tissue source for other tissue engineering approaches. The harvesting needles are made by modifying standard hypodermic needles, and they can be used alone for harvesting small amounts of tissue or coupled with a simple suction-based collection system (also made from commonly available laboratory supplies) for high-volume harvesting to facilitate studies in large animal models.

Here we describe a protocol for producing harvesting needles that can be used to collect full-thickness skin tissue without causing donor site scarring. The needles can be combined with a simple collection system to achieve high-volume harvesting.

جهاز لقطع الأنسجة ميكروكولومنس

This manuscript describes the production process for a laboratory apparatus, made from off-the-shelf components, that can be used to collect microcolumns ...

Multi-timescale Microscopy Methods for the Characterization of Fluorescently-labeled Microbubbles for Ultrasound-Triggered Drug Release

Microbubble contrast agents hold great promise for drug delivery applications with ultrasound. Encapsulating drugs in nanoparticles reduces systemic toxicity and increases circulation time of the drugs. In a novel approach to microbubble-assisted drug delivery, nanoparticles are incorporated in or on microbubble shells, enabling local and triggered release of the nanoparticle payload with ultrasound. A thorough understanding of the release mechanisms within the vast ultrasound parameter space is crucial for efficient and controlled release. This set of presented protocols is applicable to microbubbles with a shell containing a fluorescent label. Here, the focus is on microbubbles loaded with poly(2-ethyl-butyl cyanoacrylate) polymeric nanoparticles, doped with a modified Nile Red dye. The particles are fixed within a denatured casein shell. The microbubbles are produced by vigorous stirring, forming a dispersion of perfluoropropane gas in the liquid phase containing casein and nanoparticles, after which the microbubble shell self-assembles. A variety of microscopy techniques are needed to characterize the nanoparticle-stabilized microbubbles at all relevant timescales of the nanoparticle release process. Fluorescence of the nanoparticles enables confocal imaging of single microbubbles, revealing the particle distribution within the shell. In vitro ultra-high-speed imaging using bright-field microscopy at 10 million frames per second provides insight into the bubble dynamics in response to ultrasound insonation. Finally, nanoparticle release from the bubble shell is best visualized by means of fluorescence microscopy, performed at 500,000 frames per second. To characterize drug delivery in vivo, the triggered release of nanoparticles within the vasculature and their extravasation beyond the endothelial layer is studied using intravital microscopy in tumors implanted in dorsal skinfold window chambers, over a timescale of several minutes. The combination of these complementary characterization techniques provides unique insight into the behavior of microbubbles and their payload release at a range of time and length scales, both in vitro and in vivo.

The presented protocols can be used to characterize the response of fluorescently-labeled microbubbles designed for ultrasound-triggered drug delivery applications, including their activation mechanisms as well as their bioeffects. This paper covers a range of in vitro and in vivo microscopy techniques performed to capture the relevant length and timescales.

طرق المجهر متعددة الوقت لتوصيف الفقاعات الدقيقة ذات العلامات الفلورية لإطلاق المخدرات التي تسببها الموجات فوق الصوتية

Microbubble contrast agents hold great promise for drug delivery applications with ultrasound. Encapsulating drugs in nanoparticles reduces systemic ...