Tag: nanoparticles

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Two Penn Bioengineering Students Win SFB STAR Awards

Congratulations to two Bioengineering graduate students who were awarded Student Travel Achievement Recognition (STAR) Awards from the Society for Biomaterials (SFB). The STAR Award recognizes research excellence and develops future leaders within SFB and comes with a certificate and a monetary award of $250. Penn Bioengineering graduate students Rebecca Haley and Alex Hamilton, both members of the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, received their awards and presented on their research in the SFB annual meeting in April 2023.

Rebecca Haley, Ph.D. student in Bioengineering

Rebecca Haley is a Ph.D. student in Bioengineering and a NSF Graduate Research Fellow. In the Mitchell Lab, she focuses on the use of ionizable lipid nanoparticles for the delivery of protein cargos. Supported by this STAR award, she presented her work delivering small protein RAS-inhibitors that reduce cancer cell proliferation. Rebecca is interested in expanding the applications of lipid nanoparticle technology, allowing currently limited therapeutics to achieve functional delivery and, hopefully, clinical success.

Alex Hamilton, Ph.D. student in Bioengineering

Alex Hamilton is a Ph.D. student in Bioengineering and an NSF Graduate Research Fellow. Alex’s work in the Mitchell lab focuses on non-viral nucleic acid delivery. His research interests include cancer immunotherapy, vaccines, and fetal-maternal medicine. He is currently engaged in using novel high-throughput screening techniques to accelerate the discovery process for lipid nanoparticle development for a variety of disease applications.

Two more Mitchell Lab members were likewise recognized with honorable mention inn the STAR Awards: Hannah Safford, a Ph.D. student in Bioengineering and NSF Fellow, and Rohan Palanki, a M.D.-Ph.D. student in Bioengineering and NIH Fellow

Learn more about the Mitchell Lab’s research in biomaterials science, drug delivery, and cellular and molecular bioengineering in the lab’s website.

Read more stories featuring Mitchell and his team here.

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Daeyeon Lee: Evan C Thompson Lecture and American Chemical Society Award

 Daeyeon Lee, Professor and Evan C Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group, is the recipient of two recent honors.

Surrounded by his supportive research team, fellow faculty, students, School of Engineering and Applied Science Dean Vijay Kumar, and Interim Provost Beth Winkelstein, Lee recently delivered the 2023 Evan C Thompson Chair Lecture about—fittingly enough—establishing a sense of community as we return from the isolating days of the pandemic.

Daeyeon Lee of the School of Engineering and Applied Science delivers the 2023 Thompson Chair Lecture on April 4, 2023. He spoke about reconnecting in the classroom and building community.

“Students who feel connected with instructors and among peers will invest more time, work harder, and retain information better, because they feel comfortable and safe being in the classroom and making space,” Lee said in his opening remarks. “So, there are clearly lots of positive benefits to having this connectedness among students in the classroom.”

Lee’s lecture, titled “(Re)connecting in the Classroom,” was inspired by the “Great Disengagement” referenced in an article published in The Chronicle of Higher Education last year. It portrayed students as more disconnected and uncertain as they re-entered the campus environment.

Read more about Lee’s “(Re)connecting in the Classroom” in Penn Today.

In addition, Lee has received the 2022 Outstanding Achievement Award in Nanoscience from the American Chemical Society (ACS).

The annual award recognizes exceptional achievements in nanoscience research and notable leadership in the area of colloidal nanoparticles and application. Lee was chosen from a large group of extraordinary nominees among the invited speakers, “for pioneering research in development of factory-on-a-chip and its application for large scale nanoparticle synthesis and functionalization.”

Read more about this award in Penn Engineering Today.

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Toothbrushing Microbots on Walter Isaacson’s ‘Trailblazers’ Podcast

by Holly Wojcik

An infographic explains the magnetic and catalytic properties of the iron oxide nanoparticles and their assembly into bristle and floss-like forms. (Image: Melissa Pappas/Penn Engineering)

Penn Dental Medicine’s Michel Koo, Co-Director and Co-Founder of the Center for Innovation & Precision Dentistry (CiPD), was among a panel of researchers, engineers, and business founders invited to be part of a recent Trailblazers with Walter Isaacson Podcast titled “Dentistry: An Oral History of Disruption.”

Koo shared findings from one of his recent studies conducted in collaboration with Penn Engineering, which showed that a shapeshifting robotic microswarm can brush and floss teeth.

“Routine oral care is cumbersome and can pose challenges for many people, especially those who have a hard time cleaning their teeth” says Koo. “You have to brush your teeth, then floss your teeth, then rinse your mouth; it’s a manual, multistep process. The big innovation here is that the robotics system can do all three in a single, hands-free, automated way.”

The building blocks of these microrobots are iron oxide nanoparticles that have both catalytic and magnetic activity. Using a magnetic field, researchers could direct their motion and configuration to form either bristlelike structures that sweep away dental plaque from the broad surfaces of teeth, or elongated strings that can slip between teeth like a length of floss.

“Nanoparticles can be shaped and controlled with magnetic fields in surprising ways,” says Edward Steager, a senior research investigator at Penn Engineering and co-corresponding author. “We form bristles that can extend, sweep, and even transfer back and forth across a space, much like flossing. The way it works is similar to how a robotic arm might reach out and clean a surface. The system can be programmed to do the nanoparticle assembly and motion control automatically.”

Listen to “Dentistry: An Oral History of Disruption” to learn more about Toothbrushing Microbots.

This story originally appeared in Penn Engineering Today.

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Shapeshifting Microrobots Can Brush and Floss Teeth

by Katherine Unger Baillie

In a proof-of-concept study, researchers from the School of Dental Medicine and School of Engineering and Applied Science shows that a hands-free system could effectively automate the treatment and removal of tooth-decay-causing bacteria and dental plaque. (Illustration: Melissa Pappas)

A shapeshifting robotic microswarm may one day act as a toothbrush, rinse, and dental floss in one.

The technology, developed by a multidisciplinary team at the University of Pennsylvania, is poised to offer a new and automated way to perform the mundane but critical daily tasks of brushing and flossing. It’s a system that could be particularly valuable for those who lack the manual dexterity to clean their teeth effectively themselves.

The building blocks of these microrobots are iron oxide nanoparticles that have both catalytic and magnetic activity. Using a magnetic field, researchers could direct their motion and configuration to form either bristlelike structures that sweep away dental plaque from the broad surfaces of teeth, or elongated strings that can slip between teeth like a length of floss. In both instances, a catalytic reaction drives the nanoparticles to produce antimicrobials that kill harmful oral bacteria on site.

Experiments using this system on mock and real human teeth showed that the robotic assemblies can conform to a variety of shapes to nearly eliminate the sticky biofilms that lead to cavities and gum disease. The Penn team shared their findings establishing a proof-of-concept for the robotic system in the journal ACS Nano.

“Routine oral care is cumbersome and can pose challenges for many people, especially those who have hard time cleaning their teeth” says Hyun (Michel) Koo, a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in Penn’s School of Dental Medicine and co-corresponding author on the study. “You have to brush your teeth, then floss your teeth, then rinse your mouth; it’s a manual, multistep process. The big innovation here is that the robotics system can do all three in a single, hands-free, automated way.”

Read the full story in Penn Engineering Today.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in the School of Dental Medicine, co-director of the Center for Innovation & Precision Dentistry, and member of the Penn Bioengineering Graduate Group at the University of Pennsylvania.

Edward Steager is a senior research investigator in Penn’s School of Engineering and Applied Science.

Koo and Steager’s coauthors on the paper are Penn Dental Medicine’s Min Jun Oh, Alaa Babeer, Yuan Liu, and Zhi Ren and Penn Engineering’s Jingyu Wu, David A. Issadore, Kathleen J. Stebe, and Daeyeon Lee.

This work was supported in part by the National Institute for Dental and Craniofacial Research (grants DE025848 and DE029985), Procter & Gamble, and the Postdoctoral Research Program of Sungkyunkwan University.

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Bioengineering Student Savan Patel Receives the 2022 C. William Hall Scholarship

Savan Patel

Savan Patel, a junior studying Bioengineering and Finance in the Jerome Fisher Management and Technology dual degree program, was selected as the recipient of the 2022 C. William Hall Scholarship from the Society for Biomaterials. The C. William Hall Scholarship is named in honor of the Society for Biomaterials’ first president and is awarded annually “to a junior or senior undergraduate pursuing a bachelor’s degree in bioengineering or a related discipline focusing on biomaterials.” As this year’s recipient, Savan will receive complimentary membership to the Society and will have expenses paid to the Society’s annual meeting being held April 27-30, 2022 in Baltimore, Maryland.

Savan is currently a member of the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering. Savan’s research interests lie in the interface of drug delivery and immunoengineering with a particular focus on T cell delivery. His current project involves the use of modified cholesterol molecules to improve the delivery of nucleic acids (i.e., mRNA) to cell populations using lipid nanoparticles.

Lipid nanoparticles (LNPs) are a clinically proven delivery platform for nucleic acid therapeutics. One drawback of these particles is their high cellular recycling rate. Savan and the members of the Mitchell lab are working to reduce this recycling by leveraging cellular processes and incorporating modified molecules into our lipid nanoparticle formulations. The focus of Savan’s project is on modifying cholesterol, a molecule that is important to both our LNP formulations and cell membranes. The goal is to generate a more potent delivery platform to improve current therapeutics.

Following graduation, Savan intends to pursue a Ph.D. in Bioengineering.

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Penn Engineers Secure Wellcome Leap Contract for Lipid Nanoparticle Research Essential in Delivery of RNA Therapies

by Melissa Pappas

The Very Large Scale Microfluidic Integration (VLSMI) platform, a technology developed by the Penn researchers, contains hundreds of mixing channels for mass-producing mRNA-carrying lipid nanoparticles.

Penn Engineering secured a multi-million-dollar contract with Wellcome Leap under the organization’s $60 million RNA Readiness + Response (R3) program, which is jointly funded with the Coalition for Epidemic Preparedness Innovations (CEPI). Penn Engineers aim to create “on-demand” manufacturing technology that can produce a range of RNA-based vaccines.

The Penn Engineering team features Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in Chemical and Biomolecular Engineering, Michael Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, David Issadore, Associate Professor in Bioengineering and Electrical and Systems Engineering, and Sagar Yadavali, a former postdoctoral researcher in the Issadore and Lee labs and now the CEO of InfiniFluidics, a spinoff company based on their research. Drew Weissman of the Perelman School of Medicine, whose foundational research directly continued to the development of mRNA-based COVID-19 vaccines, is also a part of this interdisciplinary team.

The success of these COVID-19 vaccines has inspired a fresh perspective and wave of research funding for RNA therapeutics across a wide range of difficult diseases and health issues. These therapeutics now need to be equitably and efficiently distributed, something currently limited by the inefficient mRNA vaccine manufacturing processes which would rapidly translate technologies from the lab to the clinic.

Read more in Penn Engineering Today.

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New Lipid Nanoparticles Improve mRNA Delivery for Engineering CAR T Cells

by Melissa Pappas

The Penn researchers’ latest paper on the design of lipid nanoparticles was featured on the cover of the most recent edition of the journal Nano Letters.

From COVID vaccines to cancer immunotherapies to the potential for correcting developmental disorders in utero, mRNA-based approaches are a promising tool in the fight against a wide range of diseases. These treatments all depend on providing a patient’s cells with genetic instructions for custom proteins and other small molecules, meaning that getting those instructions inside the target cells is of critical importance.

The current delivery method of choice uses lipid nanoparticles (LNPs). Thanks to surfaces customized with binding and signaling molecules, they encapsulate mRNA sequences and smuggle them through the cell membrane. But with a practically unlimited number of variables in the makeup of those surfaces and molecules, figuring out how to design the most effective LNP is a fundamental challenge.

Now, in a study featured on the cover of the journal Nano Letters, researchers from the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine have now shown how to computationally optimize the design of these delivery vehicles.

Using an established methodology for comparing a wide range of variables known as “orthogonal design of experiments,” the researchers simultaneously tested 256 candidate LNPs. They found the frontrunner was three times better at delivering mRNA sequences into T cells than the current standard LNP formulation for mRNA delivery.

The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering in Penn’s School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.

Read the full story in Penn Engineering Today.

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Michael Mitchell Receives the 2022 SFB Young Investigator Award

by Ebonee Johnson

Michael Mitchell, Ph.D.

Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, has been awarded the 2022 Society for Biomaterials (SFB) Young Investigator Award for his “outstanding achievements in the field of biomaterials research.”

The Society for Biomaterials is a multidisciplinary society of academic, healthcare, governmental and business professionals dedicated to promoting advancements in all aspects of biomaterial science, education and professional standards to enhance human health and quality of life.

Mitchell, whose research lies at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers, is specifically being recognized for his development of the first nanoparticle RNAi therapy to treat multiple myeloma, an incurable hematologic cancer that colonizes in bone marrow.

“Before this, no one in the drug delivery field has developed an effective gene delivery system to target bone marrow,” said United States National Medal of Science recipient Robert S. Langer in Mitchell’s award citation. “Mike is a standout young investigator and leader that intimately understands the importance of research and collaboration at the interface of nanotechnology and medicine.”

Academic recipients of the SFB Young Investigator Award should not exceed the rank of Assistant Professor and must not be tenured at the time of nomination. The award includes a $1,000 endowment.

This story originally appeared in Penn Engineering Today.

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With a ‘Liquid Assembly Line,’ Penn Researchers Produce mRNA-Delivering-Nanoparticles a Hundred Times Faster than Standard Microfluidic Technologies

by Evan Lerner

Michael Mitchell, Sarah Shepherd and David Issadore pose with their new device.

The COVID vaccines currently being deployed were developed with unprecedented speed, but the mRNA technology at work in some of them is an equally impressive success story. Because any desired mRNA sequence can be synthesized in massive quantities, one of the biggest hurdles in a variety of mRNA therapies is the ability to package those sequences into the lipid nanoparticles that deliver them into cells.

Now, thanks to manufacturing technology developed by bioengineers and medical researchers at the University of Pennsylvania, a hundred-fold increase in current microfluidic production rates may soon be possible.

The researchers’ advance stems from their design of a proof-of-concept microfluidic device containing 128 mixing channels working in parallel. The channels mix a precise amount of lipid and mRNA, essentially crafting individual lipid nanoparticles on a miniaturized assembly line.

This increased speed may not be the only benefit; more precisely controlling the nanoparticles’ size could make treatments more effective. The researchers tested the lipid nanoparticles produced by their device in a mouse study, showing they could deliver therapeutic RNA sequences with four-to-five times greater activity than those made by conventional methods.

The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, and David Issadore, Associate Professor in Penn Engineering’s Department of Bioengineering, along with Sarah Shepherd, a doctoral student in both of their labs. Rakan El-Mayta, a research engineer in Mitchell’s lab, and Sagar Yadavali, a postdoctoral researcher in Issadore’s lab, also contributed to the study.

They collaborated with several researchers at Penn’s Perelman School of Medicine: postdoctoral researcher Mohamad-Gabriel Alameh, Lili Wang, Research Associate Professor of Medicine, James M. Wilson, Rose H. Weiss Orphan Disease Center Director’s Professor in the Department of Medicine, Claude Warzecha, a senior research investigator in Wilson’s lab, and Drew Weissman, Professor of Medicine and one of the original developers of the technology behind mRNA vaccines.

It was published in the journal Nano Letters.

“We believe that this microfluidic technology has the potential to not only play a key role in the formulation of current COVID vaccines,” says Mitchell, “but also to potentially address the immense need ahead of us as mRNA technology expands into additional classes of therapeutics.”

Read the full story in Penn Engineering Today.

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Modified Nanoparticles Can Stop Osteoarthritis Development

Zhiliang Cheng

As we age, the cushioning cartilage between our joints begins to wear down, making it harder and more painful to move. Known as osteoathritis, this extremely common condition has no known cure; if the symptoms can’t be managed, the affected joints must be surgically replaced.

Now, researchers are exploring whether their specially designed nanoparticles can deliver a new inflammation inhibitor to joints, targeting a previously overlooked enzyme called sPLA2.

Zhiliang Cheng, a research associate professor in the Department of Bioengineering, recently collaborated with members of Penn Medicine’s McKay Orthopaedic Research Laboratory, on a study of this approach, published in the journal Science Advances.

The normal function of sPLA2 is to provide lipids (fats) that promote a variety of inflammation processes. The enzyme is always present in cartilage tissue, but typically in low levels. However, when the researchers examined mouse and human cartilage taken from those with osteoarthritis, disproportionately high levels of the enzyme were discovered within the tissue’s structure and cells.

“This marked increase strongly suggests that sPLA2 plays a role in the development of osteoarthritis,” said the study’s corresponding author, Zhiliang Cheng, PhD, a research associate professor of Bioengineering. “Being able to demonstrate this showed that we were on the right track for what could be a potent target for the disease.”

The next step was for the study team – which included lead author Yulong Wei, MD, a researcher in Penn Medicine’s McKay Orthopaedic Research Laboratory – to put together a nanoparticle loaded with an sPLA2 inhibitor. This would block the activity of sPLA2 enzyme and, they believed, inflammation. These nanoparticles were mixed with animal knee cartilage in a lab, then observed as they diffused deeply into the dense cartilage tissue. As time progressed, the team saw that the nanoparticles stayed there and did not degrade significantly or disappear. This was important for the type of treatment the team envisioned.

Continue reading at Penn Medicine News.

Originally posted in Penn Engineering Today.