Tag Archives: Marit Mitchell

Encapsulation of proteins in nanoparticles no longer necessary for time release?

A team of researchers at the University of Toronto (Canada) have developed a technique for the therapeutic use of proteins that doesn’t require ‘nanoencapsulation’ although nanoparticles are still used according to a May 27, 2016 news item on ScienceDaily,

A U of T [University of Toronto] Engineering team has designed a simpler way to keep therapeutic proteins where they are needed for long periods of time. The discovery is a potential game-changer for the treatment of chronic illnesses or injuries that often require multiple injections or daily pills.

For decades, biomedical engineers have been painstakingly encapsulating proteins in nanoparticles to control their release. Now, a research team led by University Professor Molly Shoichet has shown that proteins can be released over several weeks, even months, without ever being encapsulated. In this case the team looked specifically at therapeutic proteins relevant to tissue regeneration after stroke and spinal cord injury.

“It was such a surprising and unexpected discovery,” said co-lead author Dr. Irja Elliott Donaghue, who first found that the therapeutic protein NT3, a factor that promotes the growth of nerve cells, was slowly released when just mixed into a Jello-like substance that also contained nanoparticles. “Our first thought was, ‘What could be happening to cause this?'”

A May 27, 2016 University of Toronto news release (also on EurekAlert) by Marit Mitchell, which originated the news item, provides more in depth explanation,

Proteins hold enormous promise to treat chronic conditions and irreversible injuries — for example, human growth hormone is encapsulated in these tiny polymeric particles, and used to treat children with stunted growth. In order to avoid repeated injections or daily pills, researchers use complicated strategies both to deliver proteins to their site of action, and to ensure they’re released over a long enough period of time to have a beneficial effect.

This has long been a major challenge for protein-based therapies, especially because proteins are large and often fragile molecules. Until now, investigators have been treating proteins the same way as small drug molecules and encapsulating them in polymeric nanoparticles, often made of a material called poly(lactic-co-glycolic acid) or PLGA.

As the nanoparticles break down, the drug molecules escape. The same process is true for proteins; however, the encapsulating process itself often damages or denatures some of the encapsulated proteins, rendering them useless for treatment. Skipping encapsulation altogether means fewer denatured proteins, making for more consistent protein therapeutics that are easier to make and store.

“This is really exciting from a translational perspective,” said PhD candidate Jaclyn Obermeyer. “Having a simpler, more reliable fabrication process leaves less room for complications with scale-up for clinical use.”

The three lead authors, Elliott Donoghue, Obermeyer and Dr. Malgosia Pakulska have shown that to get the desired controlled release, proteins only need to be alongside the PLGA nanoparticles, not inside them. …

“We think that this could speed up the path for protein-based drugs to get to the clinic,” said Elliott Donaghue.

The mechanism for this encapsulation-free controlled release is surprisingly elegant. Shoichet’s group mixes the proteins and nanoparticles in a Jello-like substance called a hydrogel, which keeps them localized when injected at the site of injury. The positively charged proteins and negatively charged nanoparticles naturally stick together. As the nanoparticles break down they make the solution more acidic, weakening the attraction and letting the proteins break free.

“We are particularly excited to show long-term, controlled protein release by simply controlling the electrostatic interactions between proteins and polymeric nanobeads,” said Shoichet. “By manipulating the pH of the solution, the size and number of nanoparticles, we can control release of bioactive proteins. This has already changed and simplified the protein release strategies that we are pursuing in pre-clinical models of disease in the brain and spinal cord.”

“We’ve learned how to control this simple phenomena,” Pakulska said. “Our next question is whether we can do the opposite—design a similar release system for positively charged nanoparticles and negatively charged proteins.”

Here’s a link to and a citation for the paper,

Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles by Malgosia M. Pakulska, Irja Elliott Donaghue, Jaclyn M. Obermeyer, Anup Tuladhar, Christopher K. McLaughlin, Tyler N. Shendruk, and Molly S. Shoichet. Science Advances  27 May 2016: Vol. 2, no. 5, e1600519 DOI: 10.1126/sciadv.1600519

This paper appears to be open access.

Dr. Molly Shoichet was featured here in a May 11, 2015 posting about the launch of her Canada-wide science communication project Research2.Reality.

Spray-on solar cells from the University of Toronto (Canada)

It’s been a while since there’s been a solar cell story from the University of Toronto (U of T) and I was starting to wonder if Ted (Edward) Sargent had moved to another educational institution. The drought has ended with the announcement of three research papers being published by researchers from Sargent’s U of T laboratory. From a Dec. 5, 2014 ScienceDaily news item,

Pretty soon, powering your tablet could be as simple as wrapping it in cling wrap.

That’s Illan Kramer’s … hope. Kramer and colleagues have just invented a new way to spray solar cells onto flexible surfaces using miniscule light-sensitive materials known as colloidal quantum dots (CQDs) — a major step toward making spray-on solar cells easy and cheap to manufacture.

A Dec. 4, 2014 University of Toronto news release (also on EurekAlert) by Marit Mitchell, which originated the news item, gives a bit more detail about the technology (Note: Links have been removed),

 Solar-sensitive CQDs printed onto a flexible film could be used to coat all kinds of weirdly-shaped surfaces, from patio furniture to an airplane’s wing. A surface the size of a car roof wrapped with CQD-coated film would produce enough energy to power three 100-watt light bulbs – or 24 compact fluorescents.

He calls his system sprayLD, a play on the manufacturing process called ALD, short for atomic layer deposition, in which materials are laid down on a surface one atom-thickness at a time.

Until now, it was only possible to incorporate light-sensitive CQDs onto surfaces through batch processing – an inefficient, slow and expensive assembly-line approach to chemical coating. SprayLD blasts a liquid containing CQDs directly onto flexible surfaces, such as film or plastic, like printing a newspaper by applying ink onto a roll of paper. This roll-to-roll coating method makes incorporating solar cells into existing manufacturing processes much simpler. In two recent papers in the journals Advanced Materials and Applied Physics Letters, Kramer showed that the sprayLD method can be used on flexible materials without any major loss in solar-cell efficiency.

Kramer built his sprayLD device using parts that are readily available and rather affordable – he sourced a spray nozzle used in steel mills to cool steel with a fine mist of water, and a few regular air brushes from an art store.

“This is something you can build in a Junkyard Wars fashion, which is basically how we did it,” says Kramer. “We think of this as a no-compromise solution for shifting from batch processing to roll-to-roll.”

“As quantum dot solar technology advances rapidly in performance, it’s important to determine how to scale them and make this new class of solar technologies manufacturable,” said Professor Ted Sargent, vice-dean, research in the Faculty of Applied Science & Engineering at University of Toronto and Kramer’s supervisor. “We were thrilled when this attractively-manufacturable spray-coating process also led to superior performance devices showing improved control and purity.”

In a third paper in the journal ACS Nano, Kramer and his colleagues used IBM’s BlueGeneQ supercomputer to model how and why the sprayed CQDs perform just as well as – and in some cases better than – their batch-processed counterparts. This work was supported by the IBM Canada Research and Development Centre, and by King Abdullah University of Science and Technology.

For those who would like to see the sprayLD device,

Here are links and citation for all three papers,

Efficient Spray-Coated Colloidal Quantum Dot Solar Cells by Illan J. Kramer, James C. Minor, Gabriel Moreno-Bautista, Lisa Rollny, Pongsakorn Kanjanaboos, Damir Kopilovic, Susanna M. Thon, Graham H. Carey, Kang Wei Chou, David Zhitomirsky, Aram Amassian, and Edward H. Sargent. Advanced Materials DOI: 10.1002/adma.201403281 Article first published online: 10 NOV 2014

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Colloidal quantum dot solar cells on curved and flexible substrates by Illan J. Kramer, Gabriel Moreno-Bautista, James C. Minor, Damir Kopilovic, and Edward H. Sargent. Appl. Phys. Lett. 105, 163902 (2014); http://dx.doi.org/10.1063/1.4898635 Published online 21 October 2014

© 2014 AIP Publishing LLC

Electronically Active Impurities in Colloidal Quantum Dot Solids by Graham H. Carey, Illan J. Kramer, Pongsakorn Kanjanaboos, Gabriel Moreno-Bautista, Oleksandr Voznyy, Lisa Rollny, Joel A. Tang, Sjoerd Hoogland, and Edward H. Sargent. ACS Nano, 2014, 8 (11), pp 11763–11769 DOI: 10.1021/nn505343e Publication Date (Web): November 6, 2014

Copyright © 2014 American Chemical Society

All three papers are behind paywalls.

Given the publication dates for the papers, this looks like an attempt to get some previously announced research noticed by sending out a summary news release using a new ‘hook’ to get attention. I hope it works for them as it must be disheartening to have your research sink into obscurity because the announcements were issued during one or more busy news cycles.

One final note, if I understand the news release correctly, this work is still largely theoretical as there don’t seem to have been any field tests.