Breaking News
June 20, 2018 - Why are vaccines less effective in the developing world?
June 20, 2018 - Study opens new window into cellular events that occur in the brain during absence seizures
June 20, 2018 - Humana and Walgreens to provide easier access to primary care and other services for seniors
June 20, 2018 - ANU research could help find life in Mars and other planets
June 20, 2018 - Multidisciplinary Human-Focused Research
June 20, 2018 - New study finds increase in use of alternative medicines among children
June 20, 2018 - Elevated NT-proBNP Found to Up Cardiovascular Risk in T2DM
June 20, 2018 - Genetics Home Reference: White-Sutton syndrome
June 20, 2018 - Canadian team reports success in transplanting hepatitis C organs
June 20, 2018 - Separating migrant children from parents at US border tantamount to child abuse
June 20, 2018 - Study finds more information about how gene linked to ASD affects the brain
June 20, 2018 - Floppy eyelids linked to sleep apnea
June 20, 2018 - Can-Fite provides update on Phase II clinical trial with drug candidate Namodenoson
June 20, 2018 - KIYATEC enrolls first patients with solid tumors in clinical study of its EV3D drug response assay
June 20, 2018 - Study finds growing support to allow pharmacists to write prescriptions
June 20, 2018 - LabConnect collaborates with Symphony to support clinical research industry
June 20, 2018 - Italian innovative SME receives 2.5 million Euro from RedSeed Ventures
June 20, 2018 - AHA: Kids Can Drown Quickly and Silently, So Prevention Is Key
June 20, 2018 - Continuous glucose monitors proven cost-effective, add to quality of life for diabetics
June 20, 2018 - Researchers use droplet-sized ‘miniecosystems’ to test therapeutic potential of molecules
June 20, 2018 - New approach could provide objective and easy-to-obtain measure of dietary adherence
June 20, 2018 - Dual-therapy approach can help boost motor recovery in stroke victims
June 20, 2018 - ‘Miracle treatment’ long-term success for babies with diabetes
June 20, 2018 - Rheumatoid Arthritis patients with depression have increased risk of disease flare
June 20, 2018 - NTU launches new research centers to prevent and treat diseases affecting Singaporeans
June 20, 2018 - Merck enters into agreement with HistoCyte Laboratories to distribute cell line reference products
June 20, 2018 - Researchers examine risk factors for opioid dependence in patients undergoing surgery for DS
June 20, 2018 - Study finds substantial variation in cardiovascular risk across India
June 20, 2018 - Kidney donation among carefully-selected older adults poses minimal risks
June 20, 2018 - Effects of atrial fibrillation can be reduced or reversed by losing weight
June 20, 2018 - Allergan’s Oral CGRP Receptor Antagonist Atogepant Demonstrates Robust Efficacy and Safety in Episodic Migraine Prevention in a Phase 2b/3 Clinical Trial
June 20, 2018 - The novel insights of proteoglycans in mineralized tissues
June 20, 2018 - Scientists shed light on key aspect of healthy cell division
June 20, 2018 - Circulating bone turnover markers not linked to hip fracture risk, shows study
June 20, 2018 - Scientists obtain key information about proteins from single human cells
June 20, 2018 - Scientists identify novel genes linked with infantile forms of schizophrenia
June 20, 2018 - Low-dose aspirin could help pregnant women with high blood pressure avoid a dangerous condition
June 20, 2018 - Unusual gene provides novel insight into how the brain wires itself
June 20, 2018 - Study finds IV acetaminophen to be no more effective than oral counterpart for colectomy patients
June 20, 2018 - MAARA to celebrate its 50th anniversary with lecture titled ‘The Future of Asthma’
June 20, 2018 - Administration eases way for small businesses to buy insurance in bulk
June 20, 2018 - High-Quality Diet May Decrease Mortality Risk in Cancer Survivors
June 20, 2018 - JAMA editorial on ECG screening and cardiac risks
June 20, 2018 - Study hints at benefits of lifestyle interventions in reducing dementia risk
June 20, 2018 - Low blood levels of vitamin D linked to increased risk of interstitial lung disease
June 20, 2018 - Simple cognitive task after brain injury improves memory function, study finds
June 20, 2018 - Clinical trial targets metastatic colorectal cancer with new combination therapy
June 20, 2018 - Researchers discover pesticide-free way to limit mosquitoes and reduce spread of West Nile virus
June 20, 2018 - Persistent psychological stress contributes to development and progression of vision loss
June 20, 2018 - Study introduces novel strategy to obtain reasonable drug cost estimates for cost-effectiveness analyses
June 20, 2018 - Does Salt Water Help Your Cut? And Other Health Myths of Summer
June 20, 2018 - Scientists help identify genetic markers for prostate cancer in global DNA download
June 19, 2018 - Common ingredient in toothpaste and hand wash could contribute to antibiotic resistance
June 19, 2018 - WHO launches multiyear campaign to eliminate use of trans fat
June 19, 2018 - Scientists could build better drugs by learning from bacteria-derived molecules
June 19, 2018 - Comparative silence between firing spikes of neurons reveals what they are really up to
June 19, 2018 - JAK inhibitors associated with aggressive lymphoma
June 19, 2018 - SetPoint announces positive long-term results of bioelectronic medicine to treat rheumatoid arthritis
June 19, 2018 - Hypnosis may help reduce fear, anxiety in children undergoing treatment for cancer
June 19, 2018 - Scientists point to potentially promising treatment target for deadly brain cancers
June 19, 2018 - After opioid overdose, only 30 percent get medicine to treat addiction
June 19, 2018 - Patients with mild Alzheimer’s disease over age 65 continue to derive benefit from DBS-f treatment
June 19, 2018 - Microbiotica partners with University of Adelaide to develop defined bacterial product for ulcerative colitis
June 19, 2018 - Paratek Presents New Analysis from Combined Phase 3 Skin Infection Studies Highlighting Efficacy of Omadacycline in Treating Drug Resistant S. aureus
June 19, 2018 - Autism is not linked to eating fish in pregnacy
June 19, 2018 - Scientists create universal assembly method to enhance cancer therapy and diagnostics
June 19, 2018 - Follow-up study confirms success of physiological test for autism
June 19, 2018 - FDA provides guidance on Novus Therapeutics’ development path for OP-02 to treat otitis media
June 19, 2018 - Scientists discover new mechanism controlling multiple sclerosis risk
June 19, 2018 - Award granted to Neem Biotech to develop antimicrobial intervention for chronic lung infections
June 19, 2018 - Study finds combined risk of death and developing cancer to be lowest in light drinkers
June 19, 2018 - Novel app teaches users how to stop life-threatening bleeding and save lives
June 19, 2018 - Single blood sample can provide adequate confirmation of diabetes
June 19, 2018 - New stimulation method increases hope for improving disorders of consciousness
June 19, 2018 - FDA Issues Complete Response Letter for Duobrii (halobetasol propionate and tazarotene) Lotion
June 19, 2018 - Defining the biology of autism
June 19, 2018 - Researchers use optogenetics to shape tissues
June 19, 2018 - Scientists discover genetic causes underlying group of related infant cancers
June 19, 2018 - Innovative digital home testing kit benefits patients with kidney conditions
June 19, 2018 - New guidance on selection and evaluation of wearable devices for use in regulatory clinical trials
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