Tag Archives: Min Chen

Nanoparticle drug delivery could reduce rejection rates for corneal transplants

I like pictures of happy researchers and, as these pictures go, the researchers seem pretty relaxed,

Caption: Qingguo Xu, D.Phil., associate professor of pharmaceutics and ophthalmology at VCU School of Pharmacy, (right) in the lab with Tuo Meng, Ph.D., (left) and Vineet Kulkarni. (School of Pharmacy) Credit: VCU School of Pharmacy

A March 23, 2023 Virginia Commonwealth University (VCU) news release (also on EurekAlert) announces work into making corneal transplants more successful, Note: A link has been removed,

Corneal transplants can be the last step to returning clear vision to many patients suffering from eye disease. Each year, approximately 80,000 corneal transplantations take place in the U.S. Worldwide, more than 184,000 corneal transplantation surgeries are performed annually. 

However, rejection rates for the corneal grafts can be as high as 10%. This is largely due to poor patient compliance to the medications, which require frequent administrations of topical eyedrops over a long period of time. 

This becomes especially acute when patients show signs of early rejection of the transplanted corneas. When this occurs, patients need to apply topical eyedrops [sic] hourly to rescue the corneal grafts from failure. 

The tedious process of eyedrop [sic] dosing causes a tremendous burden for patients. The resulting noncompliance to medication treatment can lead to even higher graft-rejection rates. 

Research led by a team at Virginia Commonwealth University may make the corneal grafts more successful by using nanoparticles to encapsulate the medication. The novel approach could significantly improve patient compliance, according to a paper recently published in Science Advances, “Six-month effective treatment of corneal graft rejection.”

Each nanoparticle encapsulates a drug called dexamethasone sodium phosphate, one of the most commonly used corticosteroids for various ocular diseases treatment such as ocular inflammation, non-infectious uveitis, macular edema and corneal neovascularization. By using the nanoparticles to control the release of the medicine over time, patients would require only one injection right after the corneal transplantation surgery without the frequent eye drops. Our studies have shown that using this method the medication maintains its efficacy for six months on a corneal graft rejection model. 

In addition, because the medicine is released slowly and directly where it is most needed, the approach requires much lower doses than current standard eyedrop treatment while providing better efficacy and safety profiles.

Qingguo Xu, D.Phil., the principal investigator of this project and an associate professor of pharmaceutics and ophthalmology at VCU School of Pharmacy, collaborated with Justin Hanes, Ph.D., the Lewis J. Ort professor of ophthalmology at Johns Hopkins University.

Xu said, “To improve patient compliance and treatment efficacy, we developed a tiny nanoparticle (around 200 nanometers) that in animal studies enables the release of the drug up to six months after a single subconjunctival injection along the eyeball.”

Tuo Meng, Ph.D., who worked on the project as a doctoral student at VCU and is the first author of this paper, said: “In our preclinical corneal graft rejection model, the single dosing of the nanoparticle successfully prevented corneal graft rejection for six months.” 

More importantly, the nanoparticle approach reversed signs of early rejection and maintained corneal grafts for six months without rejection. 

This work was supported by the National Eye Institute, National Institutes of Health, through the R01 grant R01EY027827. 

Xu’s lab focuses on developing nanotherapeutics for safer and more effective treatment of various eye diseases.

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

Six-month effective treatment of corneal graft rejection by Tuo Meng, Jinhua Zheng, Min Chen, Yang Zhao, Hadi Sudarjat, Aji Alex M.R., Vineet Kulkarni, Yumin Oh, Shiyu Xia, Zheng Ding, Hyounkoo Han, Nicole Anders, Michelle A. Rudek, Woon Chow, Walter Stark, Laura M. Ensign, Justin Hanes, and Qingguo Xu. Science Advances 22 Mar 2023 Vol 9, Issue 12 DOI: 10.1126/sciadv.adf4608

This paper is open access.

‘Nanotraps’ for catching and destroying coronavirus

‘Nanotraps’ are not vaccines although they do call the immune system into play. They represent a different way for dealing with COVID-19. (This work reminds of my June 24, 2020 posting Tiny sponges lure coronavirus away from lung cells where the researchers have a similar approach with what they call ‘nanosponges’.)

An April 27, 2021 news item on Nanowerk makes the announcement,

Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have designed a completely novel potential treatment for COVID-19: nanoparticles that capture SARS-CoV-2 viruses within the body and then use the body’s own immune system to destroy it.

These “Nanotraps” attract the virus by mimicking the target cells the virus infects. When the virus binds to the Nanotraps, the traps then sequester the virus from other cells and target it for destruction by the immune system.

In theory, these Nanotraps could also be used on variants of the virus, leading to a potential new way to inhibit the virus going forward. Though the therapy remains in early stages of testing, the researchers envision it could be administered via a nasal spray as a treatment for COVID-19.

A scanning electron microscope image of a nanotrap (orange) binding a simulated SARS-CoV-2 virus (dots in green). Scientists at the University of Chicago created these nanoparticles as a potential treatment for COVID-19. Image courtesy Chen and Rosenberg et al.

An April 27, 2021 University of Chicago news release (also on EurekAlert) by Emily Ayshford, which originated the news item, describes the work in more detail,

“Since the pandemic began, our research team has been developing this new way to treat COVID-19,” said Asst. Prof. Jun Huang, whose lab led the research. “We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential.”

Designing the perfect trap

To design the Nanotrap, the research team – led by postdoctoral scholar Min Chen and graduate student Jill Rosenberg – looked into the mechanism SARS-CoV-2 uses to bind to cells: a spike-like protein on its surface that binds to a human cell’s ACE2 receptor protein.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Similarly, they designed other nanoparticles with neutralizing antibodies on their surfaces. (These antibodies are created inside the body when someone is infected and are designed to latch onto the coronavirus in various ways).

Both ACE2 proteins and neutralizing antibodies have been used in treatments for COVID-19, but by attaching them to nanoparticles, the researchers created an even more robust system for trapping and eliminating the virus.

Made of FDA [US Food and Drug Administration]-approved polymers and phospholipids, the nanoparticles are about 500 nanometers in diameter – much smaller than a cell. That means the Nanotraps can reach more areas inside the body and more effectively trap the virus.

The researchers tested the safety of the system in a mouse model and found no toxicity. They then tested the Nanotraps against a pseudovirus – a less potent model of a virus that doesn’t replicate – in human lung cells in tissue culture plates and found that they completely blocked entry into the cells.

Once the pseudovirus bound itself to the nanoparticle – which in tests took about 10 minutes after injection – the nanoparticles used a molecule that calls the body’s macrophages to engulf and degrade the Nanotrap. Macrophages will generally eat nanoparticles within the body, but the Nanotrap molecule speeds up the process. The nanoparticles were cleared and degraded within 48 hours.

The researchers also tested the nanoparticles with a pseudovirus in an ex vivo lung perfusion system – a pair of donated lungs that is kept alive with a ventilator – and found that they completely blocked infection in the lungs.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found that their system inhibited the virus 10 times better than neutralizing antibodies or soluble ACE2 alone.

A potential future treatment for COVID-19 and beyond

Next the researchers hope to further test the system, including more tests with a live virus and on the many virus variants.

“That’s what is so powerful about this Nanotrap,” Rosenberg said. “It’s easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants.”

The Nanotraps can be stored in a standard freezer and could ultimately be given via an intranasal spray, which would place them directly in the respiratory system and make them most effective.

The researchers say it is also possible to serve as a vaccine by optimizing the Nanotrap formulation, creating an ultimate therapeutic system for the virus.

“This is the starting point,” Huang said. “We want to do something to help the world.”

The research involved collaborators across departments, including chemistry, biology, and medicine.

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

Nanotraps for the containment and clearance of SARS-CoV-2 by Min Chen, Jillian Rosenberg, Xiaolei Cai, Andy Chao Hsuan Lee, Jiuyun Shi, Mindy Nguyen, Thirushan Wignakumar, Vikranth Mirle, Arianna Joy Edobor, John Fung, Jessica Scott Donington, Kumaran Shanmugarajah, Yiliang Lin, Eugene Chang, Glenn Randall, Pablo Penaloza-MacMaster, Bozhi Tian, Maria Lucia Madariaga, Jun Huang. Matter, April 19, 2021, DOI: https://doi.org/10.1016/j.matt.2021.04.005

This paper appears to be open access.