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Posts Tagged ‘Colloidal gold’


Curator: Aviva Lev-Ari, PhD, RN

The history of gold nanoparticles in the use of advanced Medicine is about 15 years old. Dr. Barliya wrote on Diagnosing lung cancer in exhaled breath using gold  in 12/2012.nanoparticles

Alchemia commented on an MIT NEWS article on “New cardiac patch uses gold nanowires to enhance electrical signaling between cells” 9/26, 2011

I would respectfully point out that the use of almost nano sized gold particles carrying a positive electrical charge have been developed and used as ultrafine colloidal gold for over ten years and used as a treatment helping to maintain the heart’s natural rhythm, as well as for helping calm the effects of brain related limb tremors.

This ultrafine colloidal gold has also been used successfully to help calm and control the entire neural system and relieve stress related neural pain over the same past ten year period using Ultrafine Colloidal Gold by Alchemedica Intl.

It is in the light of your brilliant nano technology breakthrough, that we feel our own pioneering efforts developing and pushing the boundery in the field of ultrafine colloidal gold, silver, copper and zinc vindicated.

I salute your unorthodox approach and its successful conclusion”

http://web.mit.edu/newsoffice/2011/gold-nanowire-heart-0926.html

As an Introduction to the Genetics of Conduction Disease, we selected the following article which represents the MOST comprehensive review of the Human Cardiac Conduction System presented to date:

I. The Cardiac Conduction System

  1. David S. Park, MD, PhD;
  2. Glenn I. Fishman, MD

Circulation.2011; 123: 904-915 doi: 10.1161/​CIRCULATIONAHA.110.942284

II.  On the Genetics of the Human Conduction System

Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

III. A Promise for the MI Patient: A new cardiac patch uses Gold Nanowires to enhance Electrical Signaling between heart cells

Key term: 

Colloidal gold is a suspension (or colloid) of sub-micrometre-sized particles of gold in a fluid – usually water. The liquid is usually either an intense red colour (for particles less than 100 nm), or blue/purple (for larger particles).[1][2][3] Due to theunique optical, electronic, and molecular-recognition properties of gold nanoparticles, they are the subject of substantial research, with applications in a wide variety of areas, including electron microscopyelectronicsnanotechnology,[4][5] andmaterials science.

Properties and applications of colloidal gold nanoparticles strongly depend upon their size and shape.[6] For example, rodlike particles have both transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly.[7]

SOURCE and References for the Key term

http://en.wikipedia.org/wiki/Colloidal_gold

A heart of gold

New cardiac patch uses gold nanowires to enhance electrical signaling between cells, a promising step toward better treatment for heart-attack patients.
Emily Finn, MIT News Office 7/25/2013
March 20, 2013
A heart of gold

A scanning electron microscope (SEM) image of nanowire-alginate composite scaffolds. Star-shaped clusters of nanowires can be seen in these images.
IMAGE COURTESY OF THE DISEASE BIOPHYSICS GROUP, HARVARD UNIVERSITY
September 26, 2011
A team of researchers at MIT and Children’s Hospital Boston has built cardiac patches studded with tiny gold wires that could be used to create pieces of tissue whose cells all beat in time, mimicking the dynamics of natural heart muscle. The development could someday help people who have suffered heart attacks.The study, reported this week in Nature Nanotechnology, promises to improve on existing cardiac patches, which have difficulty achieving the level of conductivity necessary to ensure a smooth, continuous “beat” throughout a large piece of tissue.“The heart is an electrically quite sophisticated piece of machinery,” says Daniel Kohane, a professor in the Harvard-MIT Division of Health Sciences and Technology (HST) and senior author of the paper. “It is important that the cells beat together, or the tissue won’t function properly.”

The unique new approach uses gold nanowires scattered among cardiac cells as they’re grown in vitro, a technique that “markedly enhances the performance of the cardiac patch,” Kohane says. The researchers believe the technology may eventually result in implantable patches to replace tissue that’s been damaged in a heart attack.

Co-first authors of the study are MIT postdoc Brian Timko and former MIT postdoc Tal Dvir, now at Tel Aviv University in Israel; other authors are their colleagues from HST, Children’s Hospital Boston and MIT’s Department of Chemical Engineering, including Robert Langer, the David H. Koch Institute Professor.

Ka-thump, ka-thump

To build new tissue, biological engineers typically use miniature scaffolds resembling porous sponges to organize cells into functional shapes as they grow. Traditionally, however, these scaffolds have been made from materials with poor electrical conductivity — and for cardiac cells, which rely on electrical signals to coordinate their contraction, that’s a big problem.

“In the case of cardiac myocytes in particular, you need a good junction between the cells to get signal conduction,” Timko says. But the scaffold acts as an insulator, blocking signals from traveling much beyond a cell’s immediate neighbors, and making it nearly impossible to get all the cells in the tissue to beat together as a unit.

VIEW VIDEO
Video courtesy of the Disease Biophysics Group, Harvard University
Video courtesy of Youtube.com
To solve the problem, Timko and Dvir took advantage of their complementary backgrounds — Timko’s in semiconducting nanowires, Dvir’s in cardiac-tissue engineering — to design a brand-new scaffold material that would allow electrical signals to pass through.“We started brainstorming, and it occurred to me that it’s actually fairly easy to grow gold nanoconductors, which of course are very conductive,” Timko says. “You can grow them to be a couple microns long, which is more than enough to pass through the walls of the scaffold.”

From micrometers to millimeters

The team took as their base material alginate, an organic gum-like substance that is often used for tissue scaffolds. They mixed the alginate with a solution containing gold nanowires to create a composite scaffold with billions of the tiny metal structures running through it.

Then, they seeded cardiac cells onto the gold-alginate composite, testing the conductivity of tissue grown on the composite compared to tissue grown on pure alginate. Because signals are conducted by calcium ions in and among the cells, the researchers could check how far signals travel by observing the amount of calcium present in different areas of the tissue.

“Basically, calcium is how cardiac cells talk to each other, so we labeled the cells with a calcium indicator and put the scaffold under the microscope,” Timko says. There, they observed a dramatic improvement among cells grown on the composite scaffold: The range of signals conduction improved by about three orders of magnitude.

“In healthy, native heart tissue, you’re talking about conduction over centimeters,” Timko says. Previously, tissue grown on pure alginate showed conduction over only a few hundred micrometers, or thousandths of a millimeter. But the combination of alginate and gold nanowires achieved signal conduction over a scale of “many millimeters,” Timko says.

“It’s really night and day. The performance that the scaffolds have with these nanomaterials is just much, much better,” Kohane says.

“It’s very beautiful work,” says Charles Lieber, a professor of chemistry at Harvard University. “I think the results are quite unambiguous, and very exciting — both in showing fundamentally that they’ve improved the conductivity of these scaffolds, and then how that clearly makes a difference in enhancing the collective firing of the cardiac tissue.”

The researchers plan to pursue studies in vivo to determine how the composite-grown tissue functions when implanted into live hearts. Aside from implications for heart-attack patients, Kohane adds that the successful experiment “opens up a bunch of doors” for engineering other types of tissues; Lieber agrees.

“I think other people can take advantage of this idea for other systems: In other muscle cells, other vascular constructs, perhaps even in neural systems, this is a simple way to have a big impact on the collective communication of cells,” Lieber says. “A lot of people are going to be jumping on this.”

 

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Nanotechnology and MRI imaging

Author: Tilda Barliya PhD

The recent advances of “molecular and medical imaging” as an integrated discipline in academic medical centers has set the stage for an evolutionary leap in diagnostic imaging and therapy. Molecular imaging is not a substitute for the traditional process of image formation and interpretation, but is intended to improve diagnostic accuracy and sensitivity.

Medical imaging technologies allow for the rapid diagnosis and evaluation of a wide range of pathologies. In order to increase their sensitivity and utility, many imaging technologies such as CT and MRI rely on intravenously administered contrast agents. While the current generation of contrast agents has enabled rapid diagnosis, they still suffer from many undesirable drawbacks including a lack of tissue specificity and systemic toxicity issues. Through advances made in nanotechnology and materials science, researchers are now creating a new generation of contrast agents that overcome many of these challenges, and are capable of providing more sensitive and specific information (1)

Magnetic resonance imaging (MRI) contrast enhancement for molecular imaging takes advantage of superb and tunable magnetic properties of engineered magnetic nanoparticles, while a range of surface chemistry offered by nanoparticles provides multifunctional capabilities for image-directed drug delivery. In parallel with the fast growing research in nanotechnology and nanomedicine, the continuous advance of MRI technology and the rapid expansion of MRI applications in the clinical environment further promote the research in this area.

It is well known that magnetic nanoparticles, distributed in a magnetic field, create extremely large microscopic field gradients. These microscopic field gradients cause substantial diphase and shortening of longitudinal relaxation time (T1) and transverse relaxation time (T2 and T2*) of nearby nuclei, e.g., proton in the case of most MRI applications. The magnitudes of MRI contrast enhancement over clinically approved conventional gadolinium chelate contrast agents combined with functionalities of biomarker specific targeting enable the early detection of diseases at the molecular and cellular levels with engineered magnetic nanoparticles. While the effort in developing new engineered magnetic nanoparticles and constructs with new chemistry, synthesis, and functionalization approaches continues to grow, the importance of specific material designs and proper selection of imaging methods have been increasingly recognized (2)

Earlier investigations have shown that the MRI contrast enhancement by magnetic nanoparticles is highly related to their composition, size, surface properties, and the degree of aggregation in the biological environment.

Therefore, understanding the relationships between these intrinsic parameters and relaxivities of nuclei under influence of magnetic nanoparticles can provide critical information for predicting the properties of engineered magnetic nanoparticles and enhancing their performance in the MRI based theranostic applications. On the other hand, new contrast mechanisms and imaging strategies can be applied based on the novel properties of engineered magnetic nanoparticles. The most common MRI sequences, such as the spin echo (SE) or fast spin echo (FSE) imaging and gradient echo (GRE), have been widely used for imaging of magnetic nanoparticles due to their common availabilities on commercial MRI scanners. In order to minimize the artificial effect of contrast agents and provide a promising tool to quantify the amount of imaging probe and drug delivery vehicles in specific sites, some special MRI methods, such as  have been developed recently to take maximum advantage of engineered magnetic NPs

  • off-resonance saturation (ORS) imaging
  • ultrashort echo time (UTE) imaging

Because one of the major limitations of MRI is its relative low sensitivity, the strategies of combining MRI with other highly sensitive, but less anatomically informative imaging modalities such as positron emission tomography (PET) and NIRF imaging, are extensively investigated. The complementary strengths from different imaging methods can be realized by using engineered magnetic nanoparticles via surface modifications and functionalizations. In order to combine optical or nuclear with MR for multimodal imaging, optical dyes and radio-isotope labeled tracer molecules are conjugated onto the moiety of magnetic nanoparticles

Since most functionalities assembled by magnetic nanoparticles are accomplished by the surface modifications, the chemical and physical properties of nanoparticle surface as well as surface coating materials have considerable effects on the function and ability of MRI contrast enhancement of the nanoparticle core.

The longitudinal and transverse relaxivities, Ri (i=1, 2), defined as the relaxation rate per unit concentration (e.g., millimole per liter) of magnetic ions, reflects the efficiency of contrast enhancement by the magnetic nanoparticles as MRI contrast agents. In general, the relaxivities are determined, but not limited, by three key aspects of the magnetic nanoparticles:

  1. Chemical composition,
  2. Size of the particle or construct and the degree of their aggregation
  3. Surface properties that can be manipulated by the modification and functionalization.

(It is also recognized that the shape of the nanoparticles can affect the relaxivities and contrast enhancement. However these shaped particles typically have increased sizes, which may limit their in vivo applications. Nevertheless, these novel magnetic nanomaterials are increasingly attractive and currently under investigation for their applications in MRI and image-directed drug delivery).

Composition Effect: The composition of magnetic nanoparticles can significantly affect the contrast enhancing capability of nanoparticles because it dominates the magnetic moment at the atomic level. For instance, the magnetic moments of the iron oxide nanoparticles, mostly used nanoparticulate T2 weighted MRI contrast agents, can be changed by incorporating other metal ions into the iron oxide.  The composition of magnetic nanoparticles can significantly affect the contrast enhancing capability of nanoparticles because it dominates the magnetic moment at the atomic level. For instance, the magnetic moments of the iron oxide nanoparticles, mostly used nanoparticulate T2 weighted MRI contrast agents, can be changed by incorporating other metal ions into the iron oxide.

Size Effect: The dependence of relaxation rates on the particle size has been widely studied both theoretically and experimentally. Generally the accelerated diphase, often described by the R2* in magnetically inhomogeneous environment induced by magnetic nanoparticles, is predicted into two different regimes. For the relatively small nanoparticles, proton diffusion between particles is much faster than the resonance frequency shift. This resulted in the relative independence of T2 on echo time. The values for R2 and R2*are predicted to be identical. This process is called “motional averaging regime” (MAR). It has been well demonstrated that the saturation magnetization Ms increases with the particle size. A linear relationship is predicted between Ms1/3 and d-1. Therefore, the capability of MRI signal enhancement by nanoparticles correlates directly with the particle size. 

Surface Effect: MRI contrast comes from the signal difference between water molecules residing in different environments that are under the effect of magnetic nanoparticles. Because the interactions between water and the magnetic nanoparticles occur primarily on the surface of the nanoparticles, surface properties of magnetic nanoparticles play important roles in their magnetic properties and the efficiency of MRI contrast enhancement. As most biocompatible magnetic nanoparticles developed for in vivo applications need to be stabilized and functionalized with coating materials, the coating moieties can affect the relaxation of water molecules in various forms, such as diffusion, hydration and hydrogen binding.

The early investigation carried at by Duan et al suggested that hydrophilic surface coating contributes greatly to the resulted MRI contrast effect. Their study examined the proton relaxivities of iron oxide nanocrystals coated by copolymers with different levels of hydrophilicity including: poly(maleic acid) and octadecene (PMO), poly(ethylene glycol) grated polyethylenimine (PEG-g-PEI), and hyperbranched polyethylenimine (PEI). It was found that proton relaxivities of those IONPs depend on the surface hydrophilicity and coating thickness in addition to the coordination chemistry of inner capping ligands and the particle size.

The thickness of surface coating materials also contributed to the relaxivity and contrast effect of the magnetic nanoparticles. Generally, the measured T2 relaxation time increases as molecular weight of PEG increases.

In Summary

Much progress has taken place in the theranostic applications of engineered magnetic nanoparticles, especially in MR imaging technologies and nanomaterials development. As the feasibilities of magnetic nanoparticles for molecular imaging and drug delivery have been demonstrated by a great number of studies in the past decade, MRI guiding and monitoring techniques are desired to improve the disease specific diagnosis and efficacy of therapeutics. Continuous effort and development are expected to be focused on further improvement of the sensitivity and quantifications of magnetic nanoparticles in vivo for theranostics in future.

The new design and preparation of magnetic nanoparticles need to carefully consider the parameters determining the relaxivities of the nanoconstructs. Sensitive and reliable MRI methods have to be established for the quantitative detection of magnetic nanoparticles. The new generations of magnetic nanoparticles will be made not only based on the new chemistry and biological applications, but also with combined knowledge of contrast mechanisms and MRI technologies and capabilities. As new magnetic nanoparticles are available for theranostic applications, it is anticipated that new contrast mechanism and MR imaging strategies can be developed based on the novel properties of engineered magnetic nanoparticles.

References:

1http://www.omicsonline.org/2157-7439/2157-7439-2-115.php

2http://www.clinical-mri.com/pdf/CMRI/8036XXP14Ap454-472.PDF

3http://www.thno.org/v02p0086.htm

4http://www.omicsonline.org/2157-7439/2157-7439-2-115.pdf

5http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017480/

6http://www.nature.com/nmeth/journal/v7/n12/full/nmeth1210-957.html

7http://endomagnetics.com/wp-content/uploads/2011/01/TargOncol_Review_2009.pdf

8http://www.nature.com/nnano/journal/v2/n5/abs/nnano.2007.105.html

9http://www.azonano.com/article.aspx?ArticleID=2680

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