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Topic Name: Remote-control nanoparticles deliver drugs directly into tumors: Developed by MIT Scientists

Category: Nanobiotechnology

Research persons: Sangeeta Bhatia, M.D.,Ph.D., Geoff von Maltzahn

Location: Department of Electrical Engineering, MIT, United States

Details

MIT scientists have devised remotely controlled nanoparticles that, when pulsed with an electromagnetic field, release drugs to attack tumors. The innovation, reported in the Nov. 15 online issue of Advanced Materials, could lead to the improved diagnosis and targeted treatment of cancer.

In earlier work the team, led by Sangeeta Bhatia, M.D.,Ph.D., an associate professor in the Harvard-MIT Division of Health Sciences & Technology (HST) and in MIT's Department of Electrical Engineering and Computer Science, developed injectable multi-functional nanoparticles designed to flow through the bloodstream, home to tumors and clump together. Clumped particles help clinicians visualize tumors through magnetic resonance imaging (MRI).

With the ability to see the clumped particles, Bhatia’s co-author in the current work, Geoff von Maltzahn, asked the next question: “Can we talk back to them?”

The answer is yes, the team found. The system that makes it possible consists of tiny particles (billionths of a meter in size) that are superparamagnetic, a property that causes them to give off heat when they are exposed to a magnetic field. Tethered to these particles are active molecules, such as therapeutic drugs.

Exposing the particles to a low-frequency electromagnetic field causes the particles to radiate heat that, in turn, melts the tethers and releases the drugs. The waves in this magnetic field have frequencies between 350 and 400 kilohertz—the same range as radio waves. These waves pass harmlessly through the body and heat only the nanoparticles. For comparison, microwaves, which will cook tissue, have frequencies measured in gigahertz, or about a million times more powerful.

The tethers in the system consist of strands of DNA, “a classical heat sensitive material,” said von Maltzahn, a graduate student in HST. Two strands of DNA link together through hydrogen bonds that break when heated. In the presence of the magnetic field, heat generated by the nanoparticles breaks these, leaving one strand attached to the particle and allowing the other to float away with its cargo.

One advantage of a DNA tether is that its melting point is tunable. Longer strands and differently coded strands require different amounts of heat to break. This heat-sensitive tuneability makes it possible for a single particle to simultaneously carry many different types of cargo, each of which can be released at different times or in various combinations by applying different frequencies or durations of electromagnetic pulses.

To test the particles, the researchers implanted mice with a tumor-like gel saturated with nanoparticles. They placed the implanted mouse into the well of a cup-shaped electrical coil and activated the magnetic pulse. The results confirm that without the pulse, the tethers remain unbroken. With the pulse, the tethers break and release the drugs into the surrounding tissue.

The experiment is a proof of principal demonstrating a safe and effective means of tunable remote activation. However, work remains to be done before such therapies become viable in the clinic.

To heat the region, for example, a critical mass of injected particles must clump together inside the tumor. The team is still working to make intravenously injected particles clump effectively enough to achieve this critical mass.

“Our overall goal is to create multifunctional nanoparticles that home to a tumor, accumulate, and provide customizable remotely activated drug delivery right at the site of the disease,” said Bhatia.

Co-authors on the paper are Austin M. Derfus, a graduate student at the University of California at San Diego; Todd Harris, an HST graduate student; Erkki Ruoslahti and Tasmia Duza of The Burnham Institute in La Jolla, CA; and Kenneth S. Vecchio of the University of San Diego.

The research was supported by grants from the David and Lucile Packard Foundation, the National Cancer Institute of the National Institutes of Health. Dervis was supported by a G.R.E.A.T fellowship from the University of California Biotechnology Research and Educational Program.

Note for Nanoparticles

A nanoparticle (or nanopowder or nanocluster or nanocrystal) is a microscopic particle with at least one dimension less than 100 nm. Nanoparticle research is currently an area of intense scientific research, due to a wide variety of potential applications in biomedical, optical, and electronic fields. The National Nanotechnology Initiative of the United States government has driven huge amounts of state funding exclusively for nanoparticle research.
Nanoparticles are of great scientific interest as they are effectively a bridge between bulk materials and atomic or molecular structures. A bulk material should have constant physical properties regardless of its size, but at the nano-scale this is often not the case. Size-dependent properties are observed such as quantum confinement in semiconductor particles, surface plasmon resonance in some metal particles and superparamagnetism in magnetic materials.

Note for Electromagnetic field

The electromagnetic field is a physical field produced by electrically charged objects. It affects the behaviour of charged objects in the vicinity of the field.
The electromagnetic field extends indefinitely throughout space and describes the electromagnetic interaction. It is one of the four fundamental forces of nature (the others are gravitation, the weak interaction, and the strong interaction).
The field can be viewed as the combination of an electric field and a magnetic field. The electric field is produced by stationary charges, and the magnetic field by moving charges (currents); these two are often described as the sources of the field. The way in which charges and currents interact with the electromagnetic field is described by Maxwell's equations and the Lorentz Force Law.
From a classical point of view, the electromagnetic field can be regarded as a smooth, continuous field, propagated in a wavelike manner, whereas from a quantum mechanical point of view, the field can be viewed as being composed of photons.

Note for Magnetic resonance imaging

Magnetic resonance imaging (MRI), formerly referred to as magnetic resonance tomography (MRT) and, in scientific circles and as originally marketed by companies such as General Electric, nuclear magnetic resonance imaging (NMRI) or NMR zeugmatography imaging, is a non-invasive method using nuclear magnetic resonance to render images of the inside of an object. It is primarily used in medical imaging to demonstrate pathological or other physiological alterations of living tissues. MRI also has uses outside of the medical field, such as detecting rock permeability to hydrocarbons and as a non-destructive testing method to characterize the quality of products such as produce and timber.

MRI should not be confused with the NMR spectroscopy technique used in chemistry, although both are based on the same principles of nuclear magnetic resonance. In fact MRI is a series of NMR experiments applied to the signal from nuclei (typified by the hydrogen nuclei in water) used to acquire spatial information in place of chemical information about molecules. The same equipment, provided suitable probes and magnetic gradients are available, can be used for both imaging and spectroscopy.

About Researchers

Sangeeta Bhatia M.D., Ph.D. 
Director, 
Laboratory for Multiscale Regenerative Technologies 
Associate Professor 
Health Sciences and Technology/
Electrical Engineering & Computer Science, M.I.T.
Department of Medicine, 
Brigham & Women's Hospital 

M.D., Harvard Medical School; 
Ph.D., Medical Engineering, Massachusetts Institute of Technology; Harvard-MIT Division of Health Sciences and Technology; 
M.S., Mechanical Engineering, Massachusetts Institute of Technology; 
B.S., Brown University 
Joined the MIT Faculty in 2005 
E-mail: sbhatia@mit.edu