Tag Archives: University of Pennsylvania

Ultrathin, Ultralight NanoCardboard For Aerospace

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure. Now, a team of Penn Engineers has demonstrated a new material they call “nanocardboard,” an ultrathin equivalent of corrugated paper cardboard. A square centimeter of nanocardboard weighs less than a thousandth of a gram and can spring back into shape after being bent in half.

Nanocardboard is made out of an aluminum oxide film with a thickness of tens of nanometers, forming a hollow plate with a height of tens of microns. Its , similar to that of corrugated cardboard, makes it more than ten thousand times as stiff as a solid plate of the same mass.

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Nanocardboard is made out of an aluminum oxide film with a thickness of tens of nanometers, forming a hollow plate with a height of tens of microns. Its sandwich structure, similar to that of corrugated cardboard, makes it more than ten thousand times as stiff as a solid plate of the same mass. A square centimeter of nanocardboard weighs less than a thousandth of a gram and can spring back into shape after being bent in half.

Nanocardboard‘s stiffness-to-weight ratio makes it ideal for aerospace and microrobotic applications, where every gram counts. In addition to unprecedented mechanical properties, nanocardboard is a supreme thermal insulator, as it mostly consists of empty space. Future work will explore an intriguing phenomenon that results from a combination of properties: shining a light on a piece of nanocardboard allows it to levitate. Heat from the light creates a difference in temperatures between the two sides of the plate, which pushes a current of air molecules out through the bottom.

Igor Bargatin, Assistant Professor of Mechanical Engineering, along with lab members Chen Lin and Samuel Nicaise, led the study.

They published their results in the journal Nature Communications.

Source: https://phys.org/

How To Treat Congenital Disease Before Birth

For the first time, scientists have performed prenatal gene editing to prevent a lethal metabolic disorder in laboratory animals, offering the potential to treat human congenital diseases before birth. Published today in Nature Medicine, research from the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP) and offers proof-of-concept for prenatal use of a sophisticated, low-toxicity tool that efficiently edits DNA building blocks in disease-causing genes.

Using both CRISPR-Cas9 and base editor 3 (BE3) gene-editing tools, the team reduced cholesterol levels in healthy mice treated in utero by targeting a gene that regulates those levels. They also used prenatal gene editing to improve liver function and prevent neonatal death in a subgroup of mice that had been engineered with a mutation causing the lethal liver disease hereditary HT1 (HT1). HT1 in humans usually appears during infancy, and it is often treatable with a medicine called nitisinone and a strict diet. However, when treatments fail, patients are at risk of liver failure or liver cancer. Prenatal treatment could open a door to disease prevention, for HT1 and potentially for other congenital disorders.

Our ultimate goal is to translate the approach used in these proof-of-concept studies to treat severe diseases diagnosed early in pregnancy,” said study co-leader William H. Peranteau, MD, a pediatric and fetal surgeon in CHOP’s Center for Fetal Diagnosis and Treatment. “We hope to broaden this strategy to intervene prenatally in congenital diseases that currently have no effective treatment for most patients, and result in death or severe complications in infants.

We used base editing to turn off the effects of a disease-causing genetic mutation,” said study co-leader Kiran Musunuru, MD, PhD, MPH, an associate professor of Cardiovascular Medicine at Penn. “We also plan to use the same base-editing technique not just to disrupt a mutation’s effects, but to directly correct the mutation.” Musunuru is an expert in gene-editing technology and previously showed that it can be used to reduce cholesterol and fat levels in the blood, which could lead to the development of a “vaccination” to prevent cardiovascular disease.

Source: https://www.pennmedicine.org/

Red-Blood-Cell “Hitchhikers” Transport Drugs to Specific Targets

A new drug-delivery technology which uses red blood cells (RBCs) to shuttle nano-scale drug carriers, called RBC-hitchhiking (RH), has been found in animal models to dramatically increase the concentration of drugs ferried precisely to selected organs, according to a study published in Nature Communications this month by researchers from the Perelman School of Medicine at the University of Pennsylvania. This proof-of-principle study points to ways to improve drug delivery for some of the nation’s biggest killers, such as acute lung disease, stroke, and heart attack.

The vast majority of drugs fail because they spread throughout the body, landing in nearby organs where they can cause intolerable side effects, as opposed to directly targeting the areas that are really in need,” said first author Jake Brenner, MD, PhD, an assistant professor of Pulmonary Medicine and Critical Care and of Pharmacology. “By massively increasing the drug concentrations that are hitting specific tissues, the RBC hitchhikers should decrease potential side effects and improve the efficacy of drugs delivered to target organs.”

The team showed that RH can safely transport nano-scale carriers of drugs to chosen organs by targeted placement of intravascular catheters, in mice, pigs, and in ex vivo human lungs, without causing RBC or organ toxicities.

Red blood cells are a particularly attractive carrier due to their biocompatibility and known safety in transfusions,” said senior author Vladimir Muzykantov, MD, PhD, a professor of Systems Pharmacology and Translational Therapeutics. “In just a few short years since we began this work, we are now on the brink of mapping out ways to test it in clinical trials.”

The researchers found that RH drug carriers injected intravenously increased drug uptake by about 40-fold in the lungs compared to absorption of freely circulating drug carriers in blood. In addition, injecting the RH drug carriers into the carotid artery (a major blood vessel in the neck that delivers blood to the brain, neck, and face) delivers 10 percent of the injected dose to the brain, which is about 10 times higher than what is achieved through older methods such using antibodies to guide drugs to their intended targets. Such impressive drug delivery to the brain could be used to treat acute strokes, the fourth leading cause of death in the U.S.

Development of RH technology has also revealed a potentially fundamental process that hold enormous clinical promise. “The body’s largest surface area of cell-to-cell interaction is observed between red blood cells and blood vessel linings, so it is intriguing to think that our RH technology has uncovered a phenomenon in which RBCs naturally transport cargo on their surfaces,” said Muzykantov.

Source: https://www.pennmedicine.org/