After years of research, "we still treat cancer with surgery, radiation and chemotherapy," said Sangeeta Bhatia, an associate professor in MIT's Department of Electrical Engineering and Computer Science and the Harvard-MIT Division of Health Sciences and Technology. "People are now starting to think more in terms of 'Fantastic Voyage,' that sci-fi movie where they miniaturized a surgical team and injected it into someone."
The National Cancer Institute has recognized the value of Bhatia's work and has awarded her a grant to continue this line of research. Bhatia and collaborators Michael J. Sailor, chemist and materials scientist at the University of California at San Diego, and Erkki Ruoslahti, tumor biologist at the Burnham Institute for Medical Research, will receive $4.3 million in funding over five years.
The grant will allow the team to continue work on promising nanoparticle solutions that, while not quite miniature surgical teams, do have the potential to help identify tumors and deliver chemotherapy locally.
One solution already under way involves using nanoparticles for cancer imaging. By slipping through tiny gaps that exist in fast-growing tumor blood vessels and then sticking together, the particles create masses with enough of a magnetic signal to be detectable by a magnetic resonance imaging (MRI) machine. "This might allow for noninvasive imaging of fast-growing cancer 'hot spots' in tumors," said Bhatia. The team will continue this research by testing the imaging capabilities in animal models.
Another solution, described in the Jan. 16 issue of the Proceedings of the National Academy of Sciences, is a novel "homing" nanoparticle that mimics blood platelets. Platelets flow freely in the blood and act only when needed, by keying in on injured blood vessels and accumulating there to form clots. Similarly, these new nanoparticles key in on a unique feature of tumor blood vessels.
Ruoslahti had identified that the lining of tumor vessels contains a meshwork of clotted plasma proteins not found in other tissues. He also identified a peptide that binds to this meshwork. By attaching this peptide to nanoparticles, the team created a particle that targets tumors but not other tissues. When injected into the bloodstream of mice with tumors, the peptide sticks to the tumor's clotted mesh.
An unexpected feature of the nanoparticles is that they clump together and, in turn, induce more clumping. This helps to amplify the effects of the particles. "One downside of nanotechnology is that you shrink everything, including the cargo," said Bhatia. "You need particles to accumulate for them to be effective."
The assembly of these new particles concentrates them in a way that may improve on the tumor imaging capabilities the team described earlier. These particles also have the potential to be used as a means to cause clots big enough to choke off the blood supply to the tumor or to deliver drugs directly into the tumor.
But there are challenges ahead. For one, the team must verify that these particles only accumulate where they are desired. Also, they need better ways to keep the nanoparticles in the bloodstream. The body naturally clears these foreign bodies through the liver and spleen.
The team devised a means to temporarily disable this natural clearing system. They created a "decoy" particle that saturates this clearing system temporarily, allowing the active nanoparticles time to accumulate in the tumor tissue. These decoys, however, were toxic to some mice and also disable a system that normally protects the body, leaving it vulnerable to other invaders.
This challenge dovetails nicely with Bhatia's other work. Not only does she have expertise in liver functions, she directs the facility at the MIT Center for Cancer and Nanotechnology Excellence that analyzes new materials for toxicity and is working to standardize the guidelines for nanomaterial toxicity.
"We need to be able to understand the whole system better to be able to move the field forward," she said.
In addition to Sailor and Ruoslahti, Bhatia's co-authors on the recent PNAS paper are Dmitri Simberg, Tasmia Duza, Markus Essler, Jan Pilch, Lianglin Zhang and Austin M. Derfus, all from lead author Ruoslahti's laboratories at the University of California at Santa Barbara; Robert M. Hoffman, Ji Ho Park and Austin M. Derfus of the University of California at San Diego; and Meng Yang and Robert M. Hoffman of AntiCancer Inc.
The research was supported by grants from the National Cancer Institute and from the National Institutes of Health.
Elizabeth A. Thomson | MIT News Office
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy