Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > New technology can detect tiny ovarian tumors: 'Synthetic biomarkers' could be used to diagnose ovarian cancer months earlier than now possible

A high-magnification micrograph of an ovarian clear cell carcinoma. The images show, focally, the characteristic clear cells with prominent nucleoli and the typical hyaline globules. A high-magnification micrograph of an ovarian clear cell carcinoma. The images show, focally, the characteristic clear cells with prominent nucleoli and the typical hyaline globules.

Image: Nephron/CC BY-SA 3.0
A high-magnification micrograph of an ovarian clear cell carcinoma. The images show, focally, the characteristic clear cells with prominent nucleoli and the typical hyaline globules. A high-magnification micrograph of an ovarian clear cell carcinoma. The images show, focally, the characteristic clear cells with prominent nucleoli and the typical hyaline globules. Image: Nephron/CC BY-SA 3.0

Abstract:
Most ovarian cancer is diagnosed at such late stages that patients' survival rates are poor. However, if the cancer is detected earlier, five-year survival rates can be greater than 90 percent.

New technology can detect tiny ovarian tumors: 'Synthetic biomarkers' could be used to diagnose ovarian cancer months earlier than now possible

Cambridge, MA | Posted on April 10th, 2017

Now, MIT engineers have developed a far more sensitive way to reveal ovarian tumors: In tests in mice, they were able to detect tumors composed of nodules smaller than 2 millimeters in diameter. In humans, that could translate to tumor detection about five months earlier than is possible with existing blood tests, the researchers say.

The new test makes use of a "synthetic biomarker" -- a nanoparticle that interacts with tumor proteins to release fragments that can be detected in a patient's urine sample. This kind of test can generate a much clearer signal than natural biomarkers found in very small quantities in the patient's bloodstream.

"What we did in this paper is engineer our sensor to be about 15 times better than a previous version, and then compared it against a blood biomarker in a mouse model of ovarian cancer to show that we could beat it," says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and the senior author of the study.

This approach could also be adapted to work with other cancers. In this paper, which appears in the April 10 issue of Nature Biomedical Engineering, the researchers showed they can detect colorectal tumors that metastasized to the liver.

The paper's lead authors are postdoc Ester Kwon and graduate student Jaideep Dudani.

Synthetic biomarkers

Bhatia first reported the strategy of diagnosing cancer with synthetic biomarkers in 2012. This method measures the activity of protein-cutting enzymes called endoproteases, which are made by tumors to help recruit blood vessels and invade surrounding tissues so the cancer can grow and spread.

To detect this sort of enzyme, the researchers designed nanoparticles coated with small protein fragments called peptides that can be cleaved by particular proteases called MMPs. After being injected into a mouse, these particles passively collect at the tumor site. MMPs cleave the peptides to liberate tiny reporter fragments, which are then filtered out by the kidney and concentrated in the urine, where they can be detected using various methods, including a simple paper-based test.

In a paper published in 2015, the researchers created a mathematical model of this system, to understand several factors such as how the particles circulate in the body, how efficiently they encounter the protease, and at what rate the protease cleaves the peptides. This model showed that in order to detect tumors 5 millimeters in diameter or smaller in humans, the researchers would need to improve the system's sensitivity by at least one order of magnitude.

In the current study, the researchers used two new strategies to boost the sensitivity of their detector. The first was to optimize the length of the polymer that tethers the peptides to the nanoparticle. For reasons not yet fully understood, when the tether is a particular length, specific proteases cleave peptides at a higher rate. This optimization also decreases the amount of background cleavage by a nontarget enzyme.

Second, the researchers added a targeting molecule known as a tumor-penetrating peptide to the nanoparticles, which causes them to accumulate at the tumor in greater numbers and results in boosting the number of cleaved peptides that end up secreted in the urine.

By combining these two refinements, the researchers were able to enhance the sensitivity of the sensor 15-fold, which they showed was enough to detect ovarian cancer composed of small tumors (2 millimeters in diameter) in mice. They also tested this approach in the liver, where they were able to detect tumors that originated in the colon. In humans, colon cancer often spreads to the liver and forms small tumors that are difficult to detect, similar to ovarian tumors.

Earlier diagnosis

Currently, doctors can look for blood biomarkers produced by ovarian tumors, but these markers don't accumulate in great enough concentrations to be detected until the tumors are about 1 centimeter in diameter, about eight to 10 years after they form. Another diagnostic tool, ultrasound imaging, is also limited to ovarian tumors that are 1 centimeter in diameter or larger.

Being able to detect a tumor five months earlier, which the MIT researchers believe their new technique could do, could make a significant difference for some patients.

In this paper, the researchers also showed that they could detect disease proteases in microarrays of many tumor cells taken from different cancer patients. This strategy could eventually help the researchers to determine which peptides to use for different types of cancer, and even for individual patients.

"Every patient's tumor is different, and not every tumor will be amenable to targeting with the same molecule," Bhatia says. "This is a tool that will help us to exploit the modularity of the technology and personalize formulations."

The researchers are now further investigating the possibility of using this approach on other cancers, including prostate cancer, where it could be used to distinguish more aggressive tumors from those that grow much more slowly, Bhatia says.

###

The research was funded by a Koch Institute Support Grant from the National Cancer Institute, a Core Center Grant from the National Institute of Environmental Health Sciences, a Ruth L. Kirschstein National Research Service Award, a National Science Foundation Graduate Research Fellowship, the Koch Institute Marble Center for Cancer Nanomedicine, and the Howard Hughes Medical Institute.

####

For more information, please click here

Contacts:
Sarah McDonnell

617-253-8923

Copyright © Massachusetts Institute of Technology

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 News Press

News and information

Supersonic waves may help electronics beat the heat May 18th, 2018

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Disability Can Be a Superpower in Space Disabled astronauts offer unique solutions to emergencies in space May 17th, 2018

Deeper understanding of quantum chaos may be the key to quantum computers May 16th, 2018

Elastic microspheres expand understanding of embryonic development and cancer cells May 15th, 2018

Cancer

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Govt.-Legislation/Regulation/Funding/Policy

Supersonic waves may help electronics beat the heat May 18th, 2018

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Deeper understanding of quantum chaos may be the key to quantum computers May 16th, 2018

Team achieves two-electron chemical reactions using light energy, gold May 15th, 2018

Possible Futures

Supersonic waves may help electronics beat the heat May 18th, 2018

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Disability Can Be a Superpower in Space Disabled astronauts offer unique solutions to emergencies in space May 17th, 2018

Deeper understanding of quantum chaos may be the key to quantum computers May 16th, 2018

Nanomedicine

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Elastic microspheres expand understanding of embryonic development and cancer cells May 15th, 2018

Nanomedicine -- Targeting cancer cells with sugars May 14th, 2018

NanoBio Announces Corporate Name Change to BlueWillow Biologics and Closes $10M Series A Financing: Move Reflects Focus on Advancing Several Intranasal Vaccines to Human Studies May 9th, 2018

Announcements

Supersonic waves may help electronics beat the heat May 18th, 2018

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Disability Can Be a Superpower in Space Disabled astronauts offer unique solutions to emergencies in space May 17th, 2018

Deeper understanding of quantum chaos may be the key to quantum computers May 16th, 2018

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

Team achieves two-electron chemical reactions using light energy, gold May 15th, 2018

Hematene joins parade of new 2D materials: Rice University-led team extracts 3-atom-thick sheets from common iron oxide May 8th, 2018

Harvesting clean hydrogen fuel through artificial photosynthesis May 3rd, 2018

'Exceptional' research points way toward quantum discoveries: Rice University scientists make tunable light-matter couplings in nanotube films April 30th, 2018

Nanobiotechnology

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Nanomedicine -- Targeting cancer cells with sugars May 14th, 2018

NanoBio Announces Corporate Name Change to BlueWillow Biologics and Closes $10M Series A Financing: Move Reflects Focus on Advancing Several Intranasal Vaccines to Human Studies May 9th, 2018

Nanoscale measurements 100x more precise, thanks to improved two-photon technique May 8th, 2018

Research partnerships

Deeper understanding of quantum chaos may be the key to quantum computers May 16th, 2018

Nanoscale measurements 100x more precise, thanks to improved two-photon technique May 8th, 2018

Hematene joins parade of new 2D materials: Rice University-led team extracts 3-atom-thick sheets from common iron oxide May 8th, 2018

Harvesting clean hydrogen fuel through artificial photosynthesis May 3rd, 2018

Dental

MEET THE WOMAN BEHIND THE NANOTECHNOLOGY THAT REVOLUTIONIZED DENTAL CARE May 1st, 2018

A Tougher Tooth: A new dental restoration composite developed by UCSB scientists proves more durable than the conventional material August 22nd, 2017

New stem cell technique shows promise for bone repair January 25th, 2017

Nanocellulose in medicine and green manufacturing: American University professor develops method to improve performance of cellulose nanocrystals November 7th, 2016

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