Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

06 Jun 2016 - 09 Jun 2016
22 Jun 2016 - 24 Jun 2016
04 Jul 2016 - 06 Jul 2016

Targeted Nanoparticle Therapy Show Promise in Shrinking Tumors

By BiotechDaily International staff writers
Posted on 26 Apr 2012
Print article
Nanoparticles devised to zoom in on cancer cells have succeeded in shrinking tumors at lower doses than traditional chemotherapy. Targeted therapeutic nanoparticles that accumulate in tumors while bypassing healthy cells have shown promising findings in an ongoing clinical trial.

The nanoparticles contain a homing molecule that allows them to attack cancer cells exclusively, and are the first such targeted particles to enter human clinical studies. Originally developed by researchers at the Massachusetts Institute of Technology (MIT; Cambridge, MA, USA) and Brigham and Women’s Hospital (Boston, MA, USA), the particles are designed to carry the chemotherapy drug docetaxel, used to treat cancers including prostate, lung, and breast cancers.

In the study, which was published April 4, 2012, in the journal Science Translational Medicine, the researchers demonstrate the particles’ ability to target a receptor found on cancer cells and accumulate at tumor sites. The particles were also shown to be safe and effective: many of the patients’ tumors shrank as a result of the treatment, even when they received lower doses than those usually administered.

“The initial clinical results of tumor regression even at low doses of the drug validate our preclinical findings that actively targeted nanoparticles preferentially accumulate in tumors,” said Dr. Robert Langer, a professor in MIT’s department of chemical engineering and a senior author of the paper. “Previous attempts to develop targeted nanoparticles have not successfully translated into human clinical studies because of the inherent difficulty of designing and scaling up a particle capable of targeting tumors, evading the immune system, and releasing drugs in a controlled way.”

The phase I clinical trial was performed by researchers at BIND Biosciences (Cambridge, MA, USA), a company cofounded by Drs. Langer and Omid Farokhzad in 2007. “This study demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated,” stated Dr. Farokhzad, director of the laboratory of nanomedicine and biomaterials at Brigham and Women’s Hospital, associate professor of anesthesia at Harvard Medical School (Boston, MA, USA) and a senior author of the paper.

Dr. Langer’s lab started working on polymeric nanoparticles in the early 1990s, developing particles made of biodegradable materials. In the early 2000s,Drs. Langer and Farokhzad begin collaborating to develop technology that actively targets the particles to molecules found on cancer cells. By 2006, they had demonstrated that targeted nanoparticles can shrink tumors in mice, creating a way for the eventual development and evaluation of a targeted nanoparticle called BIND-014, which entered clinical trials in January 2011.

For this study, the researchers coated the nanoparticles with targeting molecules that recognize a protein called prostate-specific membrane antigen (PSMA), located abundantly on the surface of most prostate tumor cells as well as many other types of tumors.

One of the difficulties in developing effective drug-delivery nanoparticles, according to Dr. Langer, is creating them so they can perform two key functions: evading the body’s normal immune response and reaching their projected targets. “You need exactly the right combination of these properties, because if they don’t have the right concentration of targeting molecules, they won’t get to the cells you want, and if they don’t have the right stealth properties, they’ll get taken up by macrophages,” stated Dr. Langer, also a member of the David H. Koch Institute for Integrative Cancer Research at MIT.

The BIND-014 nanoparticles have three components: one that carries the drug, one that targets PSMA, and one that helps evade macrophages and other immune-system cells. A few years ago, Drs. Langer and Farokhzad developed a way to manipulate these properties very precisely, creating large collections of diverse particles that could then be evaluated for the ideal composition. “They systematically made a set of materials that varied in the properties they thought would matter, and developed a way to screen them. That’s not been done in this kind of setting before,” said Dr. Mark Saltzman, a professor of biomedical engineering at Yale University who was not involved in this study. “They’ve taken the concept from the lab into clinical trials, which is quite impressive.”

All of the particles are comprised of polymers already approved for medical use by the US Food and Drug Administration (FDA). The phase I clinical trial involved 17 patients with advanced or metastatic tumors who had already gone through traditional chemotherapy. Up to now, doses of BIND-014 have reached the amount of docetaxel usually given without nanoparticles, with no new side effects. The known side effects of docetaxel have also been milder.

In the 48 hours after treatment, the researchers found that docetaxel concentration in the patients’ blood was 100 times higher with the nanoparticles as compared to docetaxel administered in its conventional form. Higher blood concentration of BIND-014 facilitated tumor targeting resulting in tumor shrinkage in patients, in some cases with doses of BIND-014 that correspond to as low as 20% of the amount of docetaxel typically given. The nanoparticles were also effective in cancers in which docetaxel usually has little activity, including cervical cancer and cancer of the bile ducts.

The researchers also discovered that in animals treated with the nanoparticles, the concentration of docetaxel in the tumors was up to 10-fold higher than in animals treated with traditional docetaxel injection for the first 24 hours, and that nanoparticle treatment resulted in enhanced tumor reduction.

The phase I clinical trial is still ongoing and continued dose escalation is underway; BIND Biosciences is now planning phase II trials, which will further investigate the treatment’s effectiveness in a larger number of patients.

Related Links:

Massachusetts Institute of Technology
Brigham and Women’s Hospital
BIND Biosciences



Print article

Channels

Genomics/Proteomics

view channel
Image: A dark field photomicrograph showing the spirochete bacterium Borrelia burgdorferi, the pathogen responsible for causing Lyme disease (Photo courtesy of the CDC).

Statins May Help Block Transmission of Lyme Disease

A recent study found that treatment with cholesterol-lowering statins reduced the number of Borrelia burgdorferi bacteria in rodents, which helped to block transmission of Lyme disease. Lyme disease... Read more

Drug Discovery

view channel

Experimental Small-Molecule Anticancer Drug Blocks RAS-binding Domains

The experimental small-molecule anticancer drug rigosertib was shown to block tumor growth by acting as an RAS-mimetic and interacting with the RAS binding domains of RAF kinases, resulting in their inability to bind to RAS, which inhibited the RAS-RAF-MEK pathway. Oncogenic activation of RAS genes due to point mutations... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Lab Technologies

view channel

Huge Modifiable Biomedical Database to Be Available on the Wikidata Site

Genome researchers are exploiting the power of the open Internet community Wikipedia database to create a comprehensive resource for geneticists, molecular biologists, and other interested life scientists. While efficiency in generating scientific data improves almost daily, applying meaningful relationships between... Read more

Business

view channel

European Biotech Agreement to Promote Antigen-Drug Conjugation Technology

Two European biotech companies have joined forces to exploit and commercialize an innovative, site-specific ADC (antigen-drug conjugate) conjugation technology. ProBioGen (Berlin, Germany), a company specializing in the development and manufacture of complex glycoproteins and Eucodis Bioscience (Vienna, Austria), a... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.