New pulmonary fibrosis inhalation therapy shows promise in mouse model


Feature-Images-pulmonary-fibrosis-700x300Lung stem cell secretions – nanosized exosomes and secretomes – delivered via a nebulizer has been shown to help in the repair of lung injuries from pulmonary fibrosis in mice and rats in research led by a team from North Carolina State University (NC State; USA).

Pulmonary fibrosis is a fatal and incurable disease characterized by a thickening and scarring of healthy lung tissue, inflammation and replacement of lung cells with fibrotic tissue. The current treatment options for pulmonary fibrosis are severely limited and not very effective apart from highly invasive lung transplants. To rectify this, Ke Cheng of NC State led the research into developing spheroid-produced lung stem cells (LSCs) as a potential therapeutic.

“The mixture of cells in LSCs recreates the stem cells’ natural microenvironment – known as the stem cell niche – where cells secrete exosomes to communicate with each other just as they would inside your body,” Cheng explained. “LSCs secrete many beneficial proteins and growth factors known collectively as ‘secretome’ – exosomes and soluble proteins, which can reproduce the regenerative microenvironment of the cells themselves. In this work we took it one step further and tested the secretome and exosomes from our spheroid-produced stem cells against two models of pulmonary fibrosis.”

Cheng’s lab used mouse and rat models of chemically, silica- or particle-induced pulmonary fibrosis to test lung spheroid cell secretome (LSC-Sec) and lung spheroid cell exosomes (LSC-Exo) against commonly used mesenchymal stem cells (MSCs). The stem cell-derived therapeutics – proteins, small molecules and nanosized exosomes – were delivered via inhalation directly to the lungs by a nebulizer.

In the mouse model of chemically induced fibrosis, improvements were seen in all stem cell therapies compared to the control, with a 32.4% reduction in fibrosis with MSC-Sec treatment and nearly 50% reduction with LSC-Sec treatment.

In the silica-induced fibrosis mouse model LSC-Sec treatment led to a 26% reduction in fibrosis compared to 16.9% with MSC-Sec treatment.

“This work shows that lung spheroid cell secretome and exosomes are more effective than their mesenchymal stem cells counterparts in decreasing fibrotic tissue and inflammation in damaged lung tissue,” Cheng stated. “Hopefully we are taking our first steps toward an efficient, non-invasive and cost-effective way to repair damaged lungs.

“Given the therapy’s effectiveness in multiple models of lung fibrosis and inflammation, we are planning to expand the test into more pulmonary diseases, including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PH).”

“The finding that products released by lung stem cells can be just as efficacious, if not more so, than the stem cells themselves in treating pulmonary fibrosis can be a major finding that can have implications in many other diseases where stem cell therapy is being developed,” commented Kenneth Adler, Professor at NC State and a co-author of the paper.

NC State U: Faster-More Precise Silica coating process for Quantum Dot nanorods: Makes Nano-scale Semi-Conductor materials less likely to degrade – keeps optical properties.


Silica Coating for QD 072016 160711121519_1_540x360Morphological control of the silica shell on CdSe/CdS core/shell quantum dot nanorods is reported, giving single or double lobes of silica or a uniform silica shell.
Credit: Joe Tracy

Materials researchers at North Carolina State University have fine-tuned a technique that enables them to apply precisely controlled silica coatings to quantum dot nanorods in a day — up to 21 times faster than previous methods. In addition to saving time, the advance means the quantum dots are less likely to degrade, preserving their advantageous optical properties.

Quantum dots are nanoscale semiconductor materials whose small size cause them to have electron energy levels that differ from larger-scale versions of the same material. By controlling the size of the quantum dots, researchers can control the relevant energy levels — and those energy levels give quantum dots novel optical properties. These characteristics make quantum dots promising for applications such as opto-electronics and display technologies.

But quantum dots are surrounded by ligands, which are organic molecules that are sensitive to heat. If the ligands are damaged, the optical properties of the quantum dots suffer.

“We wanted to coat the rod-shaped quantum dots with silica to preserve their chemical and optical properties,” says Bryan Anderson, a former Ph.D. student at NC State who is lead author of a paper on the work. “However, coating quantum dot nanorods in a precise way poses challenges of its own.”

Previous work by other research teams has used water and ammonia in solution to facilitate coating quantum dot nanorods with silica. However, those techniques did not independently control the amounts of water and ammonia used in the process.

By independently controlling the amounts of water and ammonia used, the NC State researchers were able to match or exceed the precision of silica coatings achieved by previous methods. In addition, using their approach, the NC State team was able to complete the entire silica-coating process in a single day — rather than up to one to three weeks needed for other processes.

“The process time is important, because the longer the process takes, the more likely it is that the quantum dot nanorods being coated will degrade,” says Joe Tracy, an associate professor of materials science and engineering at NC State and senior author on the paper. “The time factor may also be important when we think about scaling this process up for manufacturing processes.”

That said, researchers still have a problem.

The process of applying the silica coating etches the cadmium sulfide surface of the quantum dot nanorods, which shortens the length of the nanorods by as much as four or five nanometers. That shortening is indicative of etching, which reduces the brightness of the light emitted by the quantum dot nanorods.

“We think ammonia may be the culprit,” Tracy says. “We have some ideas that we’re pursuing, focused on how to substitute another catalyst for ammonia in order to minimize the etching and better preserve the quantum dot nanorod’s optical properties.”

The paper, “Silica Overcoating of CdSe/CdS Core/Shell Quantum Dot Nanorods with Controlled Morphologies,” is published online in the journal Chemistry of Materials. The paper was co-authored by Wei-Chen Wu, a former Ph.D. student in Tracy’s lab. The work was done with support from the National Science Foundation under grant number DMR-1056653.

Tracy has previously published related research in Chemistry of Materials on coating gold nanorods with silica shells.


Story Source:

The above post is reprinted from materials provided by North Carolina State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Bryan D. Anderson, Wei-Chen Wu, Joseph B. Tracy. Silica Overcoating of CdSe/CdS Core/Shell Quantum Dot Nanorods with Controlled Morphologies. Chemistry of Materials, 2016; DOI: 10.1021/acs.chemmater.6b01225