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Brain Tumor

MIT Researchers Develop a Scalable Manufacturing Method for Cancer-Fighting Nanoparticles

Researchers developed a manufacturing technique that rapidly generates large quantities of nanoparticles coated with drug-delivering polymers, which hold great potential for treating cancer. The particles can be targeted directly to tumors, where they release their payload while avoiding many of the side effects of traditional chemotherapy.

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MIT engineers have made significant strides in developing a way to mass manufacture nanoparticles that can deliver cancer drugs directly to tumors. The polymer-coated particles have shown promise in treating ovarian cancer and other types of cancer, offering a more targeted approach compared to traditional chemotherapy.

Professor Paula Hammond and her team at the Massachusetts Institute of Technology (MIT) have been working on this project for over a decade. They initially used a technique known as layer-by-layer assembly to create nanoparticles with highly controlled architectures. Each layer could be embedded with drug molecules or other therapeutics, allowing the particles to target cancer cells.

However, this process was time-intensive and difficult to scale up for large-scale production. To overcome this challenge, the researchers developed an alternative approach using a microfluidic mixing device that enables the sequential addition of new polymer layers as the particles flow through a microchannel within the device.

This streamlined process eliminates the need for manual polymer mixing, streamlines production, and integrates good manufacturing practice (GMP)-compliant processes. The FDA’s GMP requirements ensure that products meet safety standards and can be manufactured in a consistent fashion.

Using this approach, the researchers can generate 15 milligrams of nanoparticles in just a few minutes, which is enough for about 50 doses. This could enable the production of more than enough particles for clinical trials and patient use.

The researchers have also demonstrated that IL-12-loaded particles manufactured using the new technique show similar performance as the original layer-by-layer nanoparticles. These nanoparticles bind to cancer tissue without entering the cancer cells, allowing them to serve as markers on the cancer cells that activate the immune system locally in the tumor.

In mouse models of ovarian cancer, this treatment can lead to both tumor growth delay and even cures. The researchers have filed for a patent on the technology and are now working with MIT’s Deshpande Center for Technological Innovation to form a company to commercialize the technology.

This scalable manufacturing method has the potential to be applied to other types of cancer, including glioblastoma. The research was funded by the U.S. National Institutes of Health, the Marble Center for Nanomedicine, the Deshpande Center for Technological Innovation, and the Koch Institute Support (core) Grant from the National Cancer Institute.

This technology could revolutionize the way cancer is treated, offering a more targeted approach that reduces side effects and improves patient outcomes. With further research and development, it has the potential to save countless lives and improve the treatment of various types of cancer.

Brain Tumor

Sleep Apnea Linked to Brain Changes and Cognitive Decline in Older Adults

Obstructive sleep apnea, a condition that causes lower oxygen levels during sleep, is linked to degeneration of brain regions associated with memory through damage to the brain’s small blood vessels, according to a new study. The study found the brain changes were strongly associated with the severity of drops in oxygen levels during rapid eye movement (REM) sleep. The study does not prove that sleep apnea causes this degeneration; it only shows an association.

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Sleep apnea, a condition that causes repeated disruptions to breathing during sleep, has been linked to cognitive decline and memory-related brain changes in older adults. A study published online in Neurology found that the severity of drops in oxygen levels during rapid eye movement (REM) sleep was strongly associated with degeneration of brain regions associated with memory.

Obstructive sleep apnea occurs when throat muscles relax during sleep, blocking the airway and causing a person to wake up repeatedly to breathe. This disrupted sleep pattern can lower oxygen levels, which in turn can damage small blood vessels in the brain.

The study included 37 people with an average age of 73 who did not have cognitive impairment. Researchers measured their oxygen levels throughout the night during all stages of sleep, including REM sleep. Participants also had brain scans to measure brain structure and took a memory test before and after sleep.

The results showed that lower oxygen levels during REM sleep were associated with higher levels of white matter hyperintensities in the brain, which can be caused by injury to small blood vessels. Having a blood oxygen level of 90% or lower is cause for concern. The study also found that having more white matter hyperintensities was linked to decreased volume and reduced thickness in areas associated with memory.

“This study may partially explain how obstructive sleep apnea contributes to cognitive decline associated with aging and Alzheimer’s disease,” said study author Bryce A. Mander, PhD. “It highlights the importance of addressing sleep disorders as a potential risk factor for cognitive decline.”

The study has some limitations, including that participants were primarily white and Asian people, so results may not be the same for other populations.

Overall, the findings suggest that sleep apnea is associated with cognitive decline and memory-related brain changes in older adults. Addressing sleep disorders and maintaining good sleep hygiene can help mitigate these risks.

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Brain Tumor

“Revolutionizing Lymphoma Treatment: Enhanced CAR T Cell Therapy Shows Promise in Small Study”

A phase I study of a next-generation CAR T cell therapy showed a 52 percent complete remission rate for patients with relapsed/refractory lymphoma.

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The article describes a groundbreaking study that has shown promising results in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, including commercially available CAR T cell therapies. The new enhanced CAR T cell therapy, dubbed huCART19-IL18, was found to be highly effective in 81% of patients and resulted in complete remission in 52%. This is a significant improvement over traditional CAR T cell therapies, which have been shown to result in long-term remission in only around 50% of patients.

The study, led by researchers at the University of Pennsylvania, used a new process that shortens the manufacturing time for the CAR T cells to just three days. This means that patients with aggressive, fast-growing cancers can begin CAR T cell therapy quicker than is currently possible with standard manufacturing times of nine to 14 days.

The addition of interleukin 18 (IL18) to the CAR T cells enhanced their ability to attack cancer cells and protected them from immune suppression and T cell exhaustion. The researchers also found that the type of CAR T cell therapy patients previously received may impact the efficacy of huCART19-IL18.

This study represents a significant development in the ongoing evolution of CAR T cell therapy, as it is the first time a cytokine-enhanced CAR T has been tested in patients with blood cancer. The researchers believe that incorporating cytokine secretion into CAR T cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers.

The study has already led to several other clinical trials being planned, including studies for acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Another trial for non-Hodgkin’s lymphoma using a similar IL18-armored CAR T cell product is currently enrolling patients. On the manufacturing side, the team is partnering with a Penn spinout company to improve the process for how these CAR T cells are created and expanded in the laboratory before being reinfused into the patient.

Overall, this study has shown promise in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, and further research is needed to fully understand its potential.

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Biochemistry

A Breakthrough in Brain Research: The Iontronic Pipette Revolutionizes Neurological Studies

Researchers have developed a new type of pipette that can deliver ions to individual neurons without affecting the sensitive extracellular milieu. Controlling the concentration of different ions can provide important insights into how individual brain cells are affected, and how cells work together. The pipette could also be used for treatments.

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The development of an iontronic pipette at Linköping University has opened up new avenues for neurological research. This innovative tool allows researchers to deliver ions directly to individual neurons without affecting the surrounding extracellular milieu. By controlling the concentration of various ions, scientists can gain valuable insights into how brain cells respond to different stimuli and interact with each other.

The human brain consists of approximately 85-100 billion neurons, supported by a similar number of glial cells that provide essential functions such as nutrition, oxygenation, and healing. The extracellular milieu, a fluid-filled space between the cells, plays a crucial role in maintaining cell function. Changes in ion concentration within this environment can activate or inhibit neuronal activity, making it essential to study how local changes affect individual brain cells.

Previous attempts to manipulate the extracellular environment involved pumping liquid into the area, disrupting the delicate biochemical balance and making it difficult to determine whether the substances themselves or the changed pressure were responsible for the observed effects. To overcome this challenge, researchers at the Laboratory of Organic Electronics developed an iontronic micropipette measuring only 2 micrometers in diameter.

This tiny pipette can deliver ions such as potassium and sodium directly into the extracellular milieu, allowing scientists to study how individual neurons respond to these changes. Glial cell activity is also monitored, providing a more comprehensive understanding of brain function.

Theresia Arbring Sjöström, an assistant professor at LOE, highlighted that glial cells are critical components of the brain’s chemical environment and can be precisely activated using this technology. In experiments conducted on mouse hippocampus tissue slices, it was observed that neurons responded dynamically to changes in ion concentration only after glial cell activity had saturated.

This research has significant implications for neurological disease treatment. The iontronic pipette could potentially be used to develop extremely precise treatments for conditions such as epilepsy, where brain function can be disrupted by localized imbalances in ion concentrations.

Researchers are now continuing their studies on chemical signaling in healthy and diseased brain tissue using the iontronic pipette. They also aim to adapt this technology to deliver medical drugs directly to affected areas of the brain, paving the way for more targeted treatments for neurological disorders.

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