Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Stanford-spawned nanoparticles home in on brain tumors, boost accuracy of surgical removal

Abstract:
Like special-forces troops laser-tagging targets for a bomber pilot, tiny particles that can be imaged three different ways at once have enabled Stanford University School of Medicine scientists to remove brain tumors from mice with unprecedented accuracy.

Stanford-spawned nanoparticles home in on brain tumors, boost accuracy of surgical removal

Stanford, CA | Posted on April 16th, 2012

In a study to be published online April 15 in Nature Medicine, a team led by Sam Gambhir, MD, PhD, professor and chair of radiology, showed that the minuscule nanoparticles engineered in his lab homed in on and highlighted brain tumors, precisely delineating their boundaries and greatly easing their complete removal. The new technique could someday help improve the prognosis of patients with deadly brain cancers.

About 14,000 people are diagnosed annually with brain cancer in the United States. Of those cases, about 3,000 are glioblastomas, the most aggressive form of brain tumor. The prognosis for glioblastoma is bleak: the median survival time without treatment is three months. Surgical removal of such tumors — a virtual imperative whenever possible — prolongs the typical patient's survival by less than a year. One big reason for this is that it is almost impossible for even the most skilled neurosurgeon to remove the entire tumor while sparing normal brain.

"With brain tumors, surgeons don't have the luxury of removing large amounts of surrounding normal brain tissue to be sure no cancer cells are left," said Gambhir, who is the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research and director of the Molecular Imaging Program at Stanford. "You clearly have to leave as much of the healthy brain intact as you possibly can."

This is a real problem for glioblastomas, which are particularly rough-edged tumors. In these tumors, tiny fingerlike projections commonly infiltrate healthy tissues, following the paths of blood vessels and nerve tracts. An additional challenge is posed by micrometastases: minuscule tumor patches caused by the migration and replication of cells from the primary tumor. Micrometastases dotting otherwise healthy nearby tissue but invisible to the surgeon's naked eye can burgeon into new tumors.

Although brain surgery today tends to be guided by the surgeon's naked eye, new molecular imaging methods could change that, and this study demonstrates the potential of using high-technology nanoparticles to highlight tumor tissue before and during brain surgery.

The nanoparticles used in the study are essentially tiny gold balls coated with imaging reagents. Each nanoparticle measures less than five one-millionths of an inch in diameter — about one-sixtieth that of a human red blood cell.

"We hypothesized that these particles, injected intravenously, would preferentially home in on tumors but not healthy brain tissue," said Gambhir, who is also a member of the Stanford Cancer Institute. "The tiny blood vessels that feed a brain tumor are leaky, so we hoped that the spheres would bleed out of these vessels and lodge in nearby tumor material." The particles' gold cores, enhanced as they are by specialized coatings, would then render the particles simultaneously visible to three distinct methods of imaging, each contributing uniquely to an improved surgical outcome.

One of those methods, magnetic resonance imaging, is already frequently used to give surgeons an idea of where in the brain the tumor resides before they operate. MRI is well-equipped to determine a tumor's boundaries, but when used preoperatively it can't perfectly describe an aggressively growing tumor's position within a subtly dynamic brain at the time the operation itself takes place.

The Gambhir team's nanoparticles are coated with gadolinium, an MRI contrast agent, in a way that keeps them stably attached to the relatively inert spheres in a blood-like environment. (In a 2011 study published in Science Translational Medicine, Gambhir and his colleagues showed in small animal models that nanoparticles similar to those used in this new study, but not containing gadolinium, were nontoxic.)

A second, newer method is photoacoustic imaging, in which pulses of light are absorbed by materials such as the nanoparticles' gold cores. The particles heat up slightly, producing detectable ultrasound signals from which a three-dimensional image of the tumor can be computed. Because this mode of imaging has high depth penetration and is highly sensitive to the presence of the gold particles, it can be useful in guiding removal of the bulk of a tumor during surgery.

The third method, called Raman imaging, leverages the capacity of certain materials (included in a layer coating the gold spheres) to give off almost undetectable amounts of light in a signature pattern consisting of several distinct wavelengths. The gold cores' surfaces amplify the feeble Raman signals so they can be captured by a special microscope.

To demonstrate the utility of their approach, the investigators first showed via various methods that the lab's nanoparticles specifically targeted tumor tissue, and only tumor tissue.

Next, they implanted several different types of human glioblastoma cells deep into the brains of laboratory mice. After injecting the imaging-enhancing nanoparticles into the mice's tail veins, they were able to visualize, with all three imaging modes, the tumors that the glioblastoma cells had spawned.

The MRI scans provided good preoperative images of tumors' general shapes and locations. And during the operation itself, photoacoustic imaging permitted accurate, real-time visualization of tumors' edges, enhancing surgical precision.

But neither MRI nor photoacoustic imaging by themselves can distinguish healthy from cancerous tissue at a sufficiently minute level to identify every last bit of a tumor. Here, the third method, Raman imaging, proved crucial. In the study, Raman signals emanated only from tumor-ensconced nanoparticles, never from nanoparticle-free healthy tissue. So, after the bulk of an animal's tumor had been cleared, the highly sensitive Raman-imaging technique was extremely accurate in flagging residual micrometastases and tiny fingerlike tumor projections still holed up in adjacent normal tissue that had been missed on visual inspection. This, in turn, enabled these dangerous remnants' removal.

"Now we can learn the tumor's extent before we go into the operating room, be guided with molecular precision during the excision procedure itself and then immediately afterward be able to 'see' once-invisible residual tumor material and take that out, too," said Gambhir, who suggested that the nanoparticles' propensity to heat up on photoacoustic stimulation, combined with their tumor specificity, might also make it possible for them to be used to selectively destroy tumors. He also expressed optimism that this kind of precision could eventually be brought to bear on other tumor types.

The study was funded by the National Institutes of Health, the National Cancer Institute's Center for Cancer Nanotechnology Excellence, the Ben and Catherine Ivy Foundation, the Canary Foundation and the Leon Levy Foundation.

Sharing first authorship were Moritz Kircher, MD, PhD, and postdoctoral scholar Adam de La Zerda, PhD. Some of the animal work was carried out through a collaboration with researchers at Memorial Sloan-Kettering Cancer Center (where Kircher is now employed) and at Weill-Cornell Medical College, both in New York City. Additional Stanford co-authors were postdoctoral scholars Jesse Jokerst, PhD, and Cristina Zavaleta, PhD; clinical instructor Erik Mitra, MD, PhD; and research scientist Frezghi Habte, PhD, all of the Department of Radiology; and Robert Sinclair, PhD, professor and chair of materials science and engineering in the School of Engineering, and his graduate student Paul Kempen.

####

About Stanford University Medical Center
The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service.

For more information, please click here

Contacts:
PRINT MEDIA CONTACT:
Bruce Goldman

650-725-2106

BROADCAST MEDIA CONTACT:
M.A. Malone
(650) 723-6912

Copyright © Stanford University Medical Center

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related Links

Information about the medical school's Department of Radiology, which also supported the work, is available at:

For more news about the school, please visit:

The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit:

Related News Press

News and information

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

JPK talks with Dr Frank Lafont, Director of the BioImaging Center Lille (BICeL) about the use of the NanoWizard® AFM together with fluorescence microscopy in the study of living cells June 19th, 2018

Imaging

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

JPK talks with Dr Frank Lafont, Director of the BioImaging Center Lille (BICeL) about the use of the NanoWizard® AFM together with fluorescence microscopy in the study of living cells June 19th, 2018

Powering the 21st Century with Integrated Photonics: UCSB-Led Team Selected for Demonstration of a Novel Waveguide Platform Which is Transparent Throughout the MWIR and LWIR Spectral Bands June 19th, 2018

Govt.-Legislation/Regulation/Funding/Policy

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

Powering the 21st Century with Integrated Photonics: UCSB-Led Team Selected for Demonstration of a Novel Waveguide Platform Which is Transparent Throughout the MWIR and LWIR Spectral Bands June 19th, 2018

Carbon nanotube optics poised to provide pathway to optical-based quantum cryptography and quantum computing: Researchers are exploring enhanced potential of carbon nanotubes for unique applications June 18th, 2018

Camouflaged nanoparticles used to deliver killer protein to cancer June 17th, 2018

Nanomedicine

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

JPK talks with Dr Frank Lafont, Director of the BioImaging Center Lille (BICeL) about the use of the NanoWizard® AFM together with fluorescence microscopy in the study of living cells June 19th, 2018

Camouflaged nanoparticles used to deliver killer protein to cancer June 17th, 2018

Graphene carpets: So neurons communicate better: Research by SISSA reveals that graphene can strengthen neuronal activity, confirming the unique properties of this nanomaterial. The study has been published on Nature Nanotechnology June 13th, 2018

Discoveries

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

Carbon nanotube optics poised to provide pathway to optical-based quantum cryptography and quantum computing: Researchers are exploring enhanced potential of carbon nanotubes for unique applications June 18th, 2018

Camouflaged nanoparticles used to deliver killer protein to cancer June 17th, 2018

Squeezing light at the nanoscale: Ultra-confined light could detect harmful molecules June 17th, 2018

Announcements

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

JPK talks with Dr Frank Lafont, Director of the BioImaging Center Lille (BICeL) about the use of the NanoWizard® AFM together with fluorescence microscopy in the study of living cells June 19th, 2018

Powering the 21st Century with Integrated Photonics: UCSB-Led Team Selected for Demonstration of a Novel Waveguide Platform Which is Transparent Throughout the MWIR and LWIR Spectral Bands June 19th, 2018

Executives Explore Key Megatrends and Innovations in MEMS, Sensors, Imaging Tech at SEMI-MSIG European Summits: Speakers to share developments in smart automotive, smart cities, smart industrial, biomedical, consumer and IoT, September 19-21, 2018 in Grenoble, France June 19th, 2018

Grants/Sponsored Research/Awards/Scholarships/Gifts/Contests/Honors/Records

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

Squeezing light at the nanoscale: Ultra-confined light could detect harmful molecules June 17th, 2018

SUNY Poly Professor Eric Lifshin Selected for ‘Fellow of the Microanalysis Society’ Position for Significant Contributions to Microanalysis June 13th, 2018

New optical sensor can determine if molecules are left or right 'handed' June 13th, 2018

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project