Breaking News
August 15, 2018 - ‘Zombie’ gene protects elephants from cancer, study finds
August 15, 2018 - Ebola outbreak in Congo spreads to active combat zone
August 15, 2018 - Study highlights pollution exposure of babies in prams
August 15, 2018 - Study provides insight into link between sleep apnea and lipid metabolism
August 15, 2018 - New study focuses on promise of gene therapy for Amish nemaline myopathy
August 15, 2018 - Researchers discover new approach to alleviate chronic itch
August 15, 2018 - Uncovering the Mysteries of MS: Medical Imaging Helps NIH Researchers Understand the Tricky Disease
August 15, 2018 - Autistic people at greater risk of becoming homeless – new research
August 15, 2018 - New imaging technique can spot tuberculosis infection in an hour
August 15, 2018 - Scientists study effects of eating breakfast versus fasting overnight before exercise
August 15, 2018 - Talking with children about suicide could save lives
August 15, 2018 - Grip strength of children predicts future cardiometabolic health
August 15, 2018 - Innovative oncofertility program launched by RMA of New York and Mount Sinai Health System
August 15, 2018 - Simple score helps predict which hospitalized heart attack patients are at high risk of readmissions
August 15, 2018 - Study shows impact of optimizing airport flight patterns on human health
August 15, 2018 - Life experiences of feeling unwanted or unplanned associated with attachment insecurity
August 15, 2018 - ACS Briefing Discusses Use of Lessons From Combat Care
August 15, 2018 - Study identifies distinct origin of ADHD in children with history of brain injury
August 15, 2018 - IgG3 antibody stops B cells from fighting pathogens in HIV patients
August 15, 2018 - Scientists discover key vulnerability of mixed lineage leukemia
August 15, 2018 - College students may experience pressures from secondary exposure to opioid abuse
August 15, 2018 - Powerful new microscope reveals inner workings of human cells with unprecedented clarity
August 15, 2018 - Married people who fight nastily more likely to suffer from leaky guts, study suggests
August 15, 2018 - Working Out After Baby – Drugs.com MedNews
August 15, 2018 - Rheumatoid Factor (RF) Test: MedlinePlus Lab Test Information
August 15, 2018 - ADHD linked to an increased risk of injury in children, study finds
August 15, 2018 - UIC researchers receive NIH funding to develop a better way to regenerate bone or tissues
August 15, 2018 - Study reveals how immune cells in the brain influence sexual behavior
August 15, 2018 - Researchers move closer to finding potential soft spot in drug-resistant tuberculosis
August 15, 2018 - Real-time dynamic monitoring of cell’s nucleus for effective cancer screening
August 15, 2018 - Lower rates of Medicare preventive care visits found in racial, ethnic minority older adults
August 15, 2018 - Scientists identify stress hormone as key factor in failure of immune system to inhibit leukemia
August 15, 2018 - Cytoplan introduces three new nutritional supplements
August 15, 2018 - Effective hemorrhage control critical for survival after motorsport accidents
August 15, 2018 - Sygnature Discovery announces ambitious expansion plan with addition of Alderley Park facility
August 15, 2018 - Dietary carbohydrates could lead to osteoarthritis, new study finds
August 15, 2018 - Male tobacco smokers have decreased number of cannabinoid CB1 receptors, study reveals
August 15, 2018 - Scientists explore ways for drug therapies to reach deadly brain tumors
August 15, 2018 - Rethinking fundamental rule of stroke care: ‘Time is brain!’
August 15, 2018 - Scientists reveal role of ‘junk DNA’ in cancer dissemination
August 15, 2018 - Google’s DeepMind AI could soon be diagnosing eye conditions
August 15, 2018 - Scientists trick the brain to embody the prosthetic limb
August 15, 2018 - Researchers focus on uncoupling obesity from diabetes
August 15, 2018 - Clinical study shows how EarlySense system effectively detects opioid-induced respiratory depression
August 15, 2018 - A class of proteins shown to be effective in reducing drug-seeking behaviors
August 15, 2018 - FundamentalVR launches first-of-its-kind SaaS software platform for surgical simulation
August 15, 2018 - Gemphire Announces Termination of Phase 2a Clinical Trial of Gemcabene in Pediatric NAFLD
August 15, 2018 - Rheumatoid arthritis in pregnancy associated with low birth weight and premature birth
August 15, 2018 - Study may help increase effectiveness of antibiotics against drug-resistant bacteria
August 15, 2018 - Analyzing resident-to-resident incidents in dementia may hold the key to reducing future fatalities
August 15, 2018 - Robotic walking frame aims to help maintain mobility of older adults
August 15, 2018 - Simple intervention during routine care reduces alcohol consumption in men with HIV
August 15, 2018 - Genetics Home Reference: gout
August 15, 2018 - Scientists ID genesis of disease, focus efforts on shape-shifting tau
August 15, 2018 - OncoThira and NDSU enter into license agreement to develop, market cancer compounds
August 15, 2018 - Scientists unravel the mystery behind ovarian cancer with high-grade serous carcinoma
August 15, 2018 - Common signs that indicate vision problems in children
August 15, 2018 - Removing the cancer label – overhaul in cancer classification proposed
August 15, 2018 - Prams may expose babies and toddlers to more air pollution finds study
August 15, 2018 - Duke researchers track missing T-cells in glioblastoma patients
August 15, 2018 - Cardiac Profiles Up With Exercise, Less Sitting in Early Old Age
August 15, 2018 - Precision medicine offers a glimmer of hope for Alzheimer’s disease
August 15, 2018 - Immunovia’s new blood-based testing platform accurately detects non-small cell lung cancer
August 15, 2018 - New method provides a ‘big picture’ of genetic influences on traits and diseases
August 15, 2018 - Early Onset Type 1 Diabetes Linked to Heart Disease, Shorter Life
August 14, 2018 - SMURF1 provides targeted approach to preventing cocaine addiction relapse
August 14, 2018 - Genetic testing pushed for hereditary high cholesterol disease
August 14, 2018 - Researchers discover new genes involved in Alzheimer’s Disease
August 14, 2018 - Medicare to overhaul ACOs but critics fear fewer participants
August 14, 2018 - Adolescent health projects receive meager percentage of global funding, study finds
August 14, 2018 - University Hospitals Seidman Cancer Center launches new CAR-T therapy trial
August 14, 2018 - In the addiction battle, is forced rehab the solution?
August 14, 2018 - Busting myths about milk – Scope
August 14, 2018 - Platelet-rich plasma does not enhance cartilage formation capabilities of stem cells
August 14, 2018 - Wearable devices and ‘mhealth’ technology emerge as promising tools for better health
August 14, 2018 - Johns Hopkins expert panel develops first set of operation-specific opioid prescribing guidelines
August 14, 2018 - Clinical study suggests new treatment direction for head and neck cancer in heavy smokers
August 14, 2018 - Phase 2 Clinical Data Published Showing Summit’s Ridinilazole Preserved Gut Microbiome of Patients with CDI
August 14, 2018 - Cardiac progenitor cells undergo a cell fate switch to build coronary arteries
August 14, 2018 - Study identifies potential guidance to treat gastric cancer patients
New drug-delivering nanoparticle could offer better way to treat brain tumors

New drug-delivering nanoparticle could offer better way to treat brain tumors

image_pdfDownload PDFimage_print

Glioblastoma multiforme, a type of brain tumor, is one of the most difficult-to-treat cancers. Only a handful of drugs are approved to treat glioblastoma, and the median life expectancy for patients diagnosed with the disease is less than 15 months.

MIT researchers have now devised a new drug-delivering nanoparticle that could offer a better way to treat glioblastoma. The particles, which carry two different drugs, are designed so that they can easily cross the blood-brain barrier and bind directly to tumor cells. One drug damages tumor cells’ DNA, while the other interferes with the systems cells normally use to repair such damage.

In a study of mice, the researchers showed that the particles could shrink tumors and prevent them from growing back.

“What is unique here is we are not only able to use this mechanism to get across the blood-brain barrier and target tumors very effectively, we are using it to deliver this unique drug combination,” says Paula Hammond, a David H. Koch Professor in Engineering, the head of MIT’s Department of Chemical Engineering, and a member of MIT’s Koch Institute for Integrative Cancer Research.

Hammond and Scott Floyd, a former Koch Institute clinical investigator who is now an associate professor of radiation oncology at Duke University School of Medicine, are the senior authors of the paper, which appears in Nature Communications. The paper’s lead author is Fred Lam, a Koch Institute research scientist.

Targeting the brain

The nanoparticles used in this study are based on particles originally designed by Hammond and former MIT graduate student Stephen Morton, who is also an author of the new paper. These spherical droplets, known as liposomes, can carry one drug in their core and the other in their fatty outer shell.

To adapt the particles to treat brain tumors, the researchers had to come up with a way to get them across the blood-brain barrier, which separates the brain from circulating blood and prevents large molecules from entering the brain.

The researchers found that if they coated the liposomes with a protein called transferrin, the particles could pass through the blood-brain barrier with little difficulty. Furthermore, transferrin also binds to proteins found on the surface of tumor cells, allowing the particles to accumulate directly at the tumor site while avoiding healthy brain cells.

This targeted approach allows for delivery of large doses of chemotherapy drugs that can have unwanted side effects if injected throughout the body. Temozolomide, which is usually the first chemotherapy drug given to glioblastoma patients, can cause bruising, nausea, and weakness, among other side effects.

Building on prior work from Floyd and Yaffe on the DNA-damage response of tumors, the researchers packaged temozolomide into the inner core of the liposomes, and in the outer shell they embedded an experimental drug called a bromodomain inhibitor. Bromodomain inhibitors are believed to interfere with cells’ ability to repair DNA damage. By combining these two drugs, the researchers created a one-two punch that first disrupts tumor cells’ DNA repair mechanisms, then launches an attack on the cells’ DNA while their defenses are down.

The researchers tested the nanoparticles in mice with glioblastoma tumors and showed that after the nanoparticles reach the tumor site, the particles’ outer layer degrades, releasing the bromodomain inhibitor JQ-1. About 24 hours later, temozolomide is released from the particle core.

The researchers’ experiments revealed that drug-delivering nanoparticles coated with transferrin were far more effective at shrinking tumors than either uncoated nanoparticles or temozolomide and JQ-1 injected into the bloodstream on their own. The mice treated with the transferrin-coated nanoparticles survived for twice as long as mice that received other treatments.

“This is yet another example where the combination of nanoparticle delivery with drugs involving the DNA-damage response can be used successfully to treat cancer,” says Michael Yaffe, a David H. Koch Professor of Science and member of the Koch Institute, who is also an author of the paper.

Novel therapies

In the mouse studies, the researchers found that animals treated with the targeted nanoparticles experienced much less damage to blood cells and other tissues normally harmed by temozolomide. The particles are also coated with a polymer called polyethylene glycol (PEG), which helps protect the particles from being detected and broken down by the immune system. PEG and all of the other components of the liposomes are already FDA-approved for use in humans.

“Our goal was to have something that could be easily translatable, by using simple, already approved synthetic components in the liposome,” Lam says. “This was really a proof-of-concept study [showing] that we can deliver novel combination therapies using a targeted nanoparticle system across the blood-brain barrier.”

JQ-1, the bromodomain inhibitor used in this study, would likely not be well-suited for human use because its half-life is too short, but other bromodomain inhibitors are now in clinical trials.

The researchers anticipate that this type of nanoparticle delivery could also be used with other cancer drugs, including many that have never been tried against glioblastoma because they couldn’t get across the blood-brain barrier.

“Because there’s such a short list of drugs that we can use in brain tumors, a vehicle that would allow us to use some of the more common chemotherapy regimens in brain tumors would be a real game-changer,” Floyd says. “Maybe we could find efficacy for more standard chemotherapies if we can just get them to the right place by working around the blood-brain barrier with a tool like this.”

Source:

http://news.mit.edu/2018/tiny-particles-could-help-fight-brain-cancer-0524

Tagged with:

About author

Related Articles