Skin Patches Melt Fat

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders, such as obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina. Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat—a process named browning—which can happen naturally when the body is exposed to cold temperatures—as a treatment for obesity and diabetes.


There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology & cell biology at Columbia. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter—too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

The findings, from experiments in mice, were published online today in ACS Nano.


Understanding The Risks Of Nanotechnology

When radioactive materials were first introduced into society, it took a while before scientists understood the risks. The same is true of nanotechnology today, according to Dr Vladimir Baulin, from University Rovira i Virgili, in Tarragona, Spain, who together with colleagues has shown for the first time how nanoparticles can cross biological – or lipidmembranes in a paper published in the journal Science Advances
Nanotechnology is all around us, in building materials, in toothpaste and in cleaning products. Across Europe, hundreds of institutions are working together to look at how to monitor exposure, manage the risks and advise on what regulations may be needed under the EU’s NanoSafety Cluster.

nanoparticles effects on lipids

This is the first observation to show directly how tiny gold nanoparticles can cross a lipid bilayer (main part of a biological membrane). This process was quantified and the time of each step was estimated. The lipid membrane is the ultimate barrier protecting cells from the outside environment and if the nanoparticles can cross this barrier they may go into cells.’

‘Dr Jean-Baptiste Fleury (from Saarland University in Germany) designed a special set-up with two chambers separated by a lipid bilayer, which contained fluorescent lipids (fat molecules). Non-fluorescent nanoparticles were added to only one of the chambers. In this set-up, nanoparticles became visible only when they touched the fluorescent bilayer and exchanged lipids with it. If one sees the fluorescent nanoparticle in the second chamber, this means it was in contact with the bilayer and it crossed the bilayer from one chamber to another. This was the proof. In addition, the process of translocation was quantified and the time of the crossing was estimated as milliseconds.’

All biological objects, biomolecules, proteins that exist in living organisms evolved over billions of years to adapt to each other. Nanoparticles which are synthesised in the laboratory are thus considered by a living organism as something foreign. It is a big challenge to make them compatible and not toxic.’ ‘I would count the applications of nanoparticles as starting from the 1985 Nobel Prize for the discovery of fullerenes (molecules of hollow football-shaped carbon). This was the start of the nanoparticle boom.’

This is becoming urgent because nanoparticles and nanotechnology in general are entering our lives. Now it is possible to synthesise nanomaterials with precise control, fabricate nanostructures on surfaces and do precise tailoring of the properties of nanoparticles.

‘It is becoming quite urgent to understand the exact mechanisms of nanotoxicity and make a classification depending on the mechanism. Radioactivity or X-rays entered our lives the same way. It took time until researchers understood the mechanisms of action on living organisms and the regulations evolved with our understanding.’

gold nanoparticles cross the membrane

This is the first observation to show directly how tiny gold nanoparticles can cross a lipid bilayer.

An empirical test of toxicity is that you put nanoparticles into the cells and you see the cells are dead, but you don’t understand what has happened, this is empirical. This is a legitimate tool, but it is not enough to address toxicity. Instead, one could start from the properties of nanoparticles and think about classifying nano-objects based on their physical or chemical properties by trying to predict the effect of a given nanoparticle on a cell or tissue beforehand.

I understand, it may look too ambitious, since there are a lot of tiny details that are not considered at the moment in theoretical models or any classification. However, even if it may not be exact, it can give some guidance and it would be possible to make predictions on how nanoparticles and polymers interact with lipid membranes. For example, in this study we used theoretical modelling to suggest the size and surface properties of the nanoparticle that is able to cross the lipid membrane through a certain pathway and it was observed experimentally.’


Obesity: How To Burn Fat

Researchers at MIT and Brigham and Women’s Hospital have developed nanoparticles that can deliver antiobesity drugs directly to fat tissue. Overweight mice treated with these nanoparticles lost 10 percent of their body weight over 25 days, without showing any negative side effects. The drugs work by transforming white adipose tissue, which is made of fat-storing cells, into brown adipose tissue, which burns fat. The drugs also stimulate the growth of new blood vessels in fat tissue, which positively reinforces the nanoparticle targeting and aids in the white-to-brown transformation. These drugs, which are not FDA-approved to treat obesity, are not new, but the research team developed a new way to deliver them so that they accumulate in fatty tissues, helping to avoid unwanted side effects in other parts of the body.


The advantage here is now you have a way of targeting it to a particular area and not giving the body systemic effects. You can get the positive effects that you’d want in terms of antiobesity but not the negative ones that sometimes occur,” says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.

More than one-third of Americans are considered to be obese, and last year obesity overtook smoking as the top preventable cause of cancer death in the United States, with 20 percent of the 600,000 cancer deaths attributed to obesity.

Langer and Omid Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital, are the senior authors of the study, which appears in theProceedings of the National Academy of Sciences the week of May 2. The paper’s lead authors are former MIT postdoc Yuan Xue and former BWH postdoc Xiaoyang Xu.


NanoDrones Destroy Fat In Arteries

Nanometer-sized “drones” will deliver a special type of healing molecule to fat deposits in arteries. This is new approach to prevent heart attacks caused by atherosclerosis, according to a study in pre-clinical models by scientists at Brigham and Women’s Hospital (BWH) and Columbia University Medical Center.

Although current treatments have reduced the number of deaths from atherosclerosis-related disease, atherosclerosis remains a dangerous health problem: Atherosclerosis of the coronary arteries is the #1 killer of women and men in the U.S., resulting in one out of every four deaths. In the study, targeted biodegradable nanodrones’ that delivered a special type of drug that promotes healing (‘resolution‘) successfully restructured atherosclerotic plaques in mice to make them more stable. This remodeling of the plaque environment would be predicted in humans to block plaque rupture and thrombosis and thereby prevent heart attacks and strokes.
nanodronesNanometer-sized ‘drones’ that deliver a special type of healing molecule to fat deposits in arteries could become a new way to prevent heart attacks caused by atherosclerosis
This is the first example of a targeted nanoparticle technology that reduces atherosclerosis in an animal model,” said co-senior author Omid Farokhzad, MD, associate professor and director of the Laboratory of Nanomedicine and Biomaterials at BWH and Harvard Medical School (HMS). “Years of research and collaboration have culminated in our ability to use nanotechnology to resolve inflammation, remodel and stabilize plaques in a model of advanced atherosclerosis.”

These findings are published in the February 18th online issue of Science Translational Medicine.