WebZine
2019. 11
What's New
A better candidate for chemo delivery
Drug-loaded nanoparticles bound to circulating red blood cells inhibit lung cancer metastasis
Lindsay Brownell | Wyss Institute Communications
This scanning electron microscope image shows drug-loaded nanoparticles bound to mouse erythrocytes (red blood cells).
Wyss Institute at Harvard University
Chemotherapy has been the backbone of cancer treatment for decades, but it is notorious for its toxicity to healthy cells, severe side effects, and poor targeting of the intended tumors.
Efforts to improve chemotherapy’s efficacy and tolerability include packaging drugs into nanoparticles, which can protect them from degradation in the body, control their release pattern, and shield the patient from some of the drugs’ side effects.
However, nanoparticles have so far failed to show significant accumulation in target sites, even when they are engineered with surface proteins designed to bind to specific tissues, largely because they are quickly cleared from the blood by the liver and spleen.
Now, a new technique called ELeCt (erythrocyte-leveraged chemotherapy) developed at Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) aims to resolve those problems by using a Trojan horse, smuggling drug-loaded nanoparticles into cancerous lung tissue by mounting them onto the body’s own erythrocytes, commonly called red blood cells. When the red blood cells make their tight squeeze through the lung’s tiny capillaries, the nanoparticles are sheared off and taken up by lung cells with 10-fold greater success than free-floating nanoparticles, and dramatically improve the survival of mice with lung cancer metastasis. The research is reported in Science Advances.
“Thirty to 55 percent of patients with advanced cancer have metastasis to the lung, due to its large number of capillaries, and there is currently no treatment for lung metastasis itself,” said co-first author Zongmin Zhao, postdoctoral fellow in the lab of Samir Mitragotri at the Wyss Institute and SEAS. “ELeCt exploits those same blood vessels to effectively deliver drugs that fight lung metastasis, and has strong potential to be developed into a clinical treatment.”
To create the ELeCt system, Zhao and his collaborators loaded doxorubicin, a common cancer chemotherapy drug, into tiny nanoparticles composed of a biodegradable polymer called PLGA. They then incubated the nanoparticles with both mouse and human erythrocytes, and found that they bound to the cells’ surfaces with high efficiency and without damaging them, allowing the dose of the drug carried by the erythrocytes to be tuned to fit different required dosages.
Example environment from the virtual reality display
Credit: University of Cambridge
Virtual reality (VR) can identify early Alzheimer’s disease more accurately than ‘gold standard’ cognitive tests currently in use, suggests new research from the University of Cambridge.
The study highlights the potential of new technologies to help diagnose and monitor conditions such as Alzheimer’s disease, which affects more than 525,000 people in the UK.
In 2014, Professor John O’Keefe of UCL was jointly awarded the Nobel Prize in Physiology or Medicine for ‘discoveries of cells that constitute a positioning system in the brain’. Essentially, this means that the brain contains a mental ‘satnav’ of where we are, where we have been, and how to find our way around.
A key component of this internal satnav is a region of the brain known as the entorhinal cortex. This is one of the first regions to be damaged in Alzheimer’s disease, which may explain why ‘getting lost’ is one of the first symptoms of the disease. However, the pen-and-paper cognitive tests used in clinic to diagnose the condition are unable to test for navigation difficulties.
In collaboration with Professor Neil Burgess at UCL, a team of scientists at the Department of Clinical Neurosciences at the University of Cambridge led by Dr Dennis Chan, previously Professor O’Keefe’s PhD student, developed and trialled a VR navigation test in patients at risk of developing dementia. The results of their study are published today in the journal Brain.
In the test, a patient dons a VR headset and undertakes a test of navigation while walking within a simulated environment. Successful completion of the task requires intact functioning of the entorhinal cortex, so Dr Chan’s team hypothesised that patients with early Alzheimer’s disease would be disproportionately affected on the test.
The team recruited 45 patients with mild cognitive impairment (MCI) from the Cambridge University Hospitals NHS Trust Mild Cognitive Impairment and Memory Clinics, supported by the Windsor Research Unit at Cambridgeshire and Peterborough NHS Foundation Trust. Patients with MCI typically exhibit memory impairment, but while MCI can indicate early Alzheimer’s, it can also be caused by other conditions such as anxiety and even normal aging. As such, establishing the cause of MCI is crucial for determining whether affected individuals are at risk of developing dementia in the future.