Cancer Killing Nanoparticles Home in on Their Target
January 2014 | eNews
While cytotoxic chemotherapy remains the cornerstone of most cancer treatment, therapeutic approaches are becoming ever more targeted, with the goal of killing cancer cells while avoiding damage to healthy cells. Recent years have seen the development and approval of an array of targeted therapies, including monoclonal antibodies and small molecule inhibitors, directed towards proteins expressed on the surface of cancer cells or to molecular changes within cancer cells. However, these approaches, like chemotherapy, are still associated with dose-limiting toxicities. A potential approach to this problem is the use of nanoparticles designed to deliver the drug directly to cancer cells, in a controlled manner.
Omid Farokhzad, MD, Principal Investigator in the Laboratory of Nanomedicine and Biomaterials at Harvard Medical School has been involved in developing a variety of nanotechnologies for medical applications. “A big thrust of our work has been to develop targeted nanoparticles for treatment of cancers,” he explains. “The idea is that we can put drugs in biodegradable polymeric nanoparticles and decorate the surface of the nanoparticles with ligands that can recognize tumor antigen."
Nanoparticles Now in Clinical Trials
In collaboration with Philip Kantoff, MD (DFCI), Robert Langer (Koch Institute/MIT) and researchers at BIND Therapeutics, Farokzhad and colleagues are clinically testing targeted nanoparticles in humans. Specifically, researchers are evaluating an agent called BIND-014 in Phase 2 clinical trials in patients with metastatic castration-resistant prostate cancer and non-small cell lung cancer.
BIND-014 consists of a stable small molecule ligand displayed on a nanoparticle surface that is directed towards prostate-specific membrane antigen (PSMA), an antigen present in prostate cancers and also in the neovasculature of other types of solid tumors. By targeting PSMA, BIND-014 delivers docetaxel more precisely into the targeted cells. In the clinical trials, patients receive an intravenous infusion of BIND-014 every 3 weeks.
Finding a Needle in a Haystack
To single out BIND-014, the researchers screened libraries of nanoparticles with many different combinations of characteristics. BIND-014 circulates longer before being cleared than many other nanoparticles, thus, allowing the accumulation of much higher concentrations of docetaxel in the plasma surrounding the cancer cells—perhaps 1,000 times higher—compared with conventional docetaxel.
The early development of this combinatorial screening platform, says Farokhzad, started with funding from the DF/HCC Prostate Cancer SPORE, led by Kantoff. “This gave us the ability to develop high-throughput approaches for synthesizing and screening targeted nanoparticles.” Subsequently the Prostate Cancer Foundation and others have made a very large commitment to this work. “It's been a very fruitful collaboration spanning over 10 years now,” he says.
Future Directions: Evaluating Nanoparticle Safety and Developing New Formulations
According to Farokhzad, the safety profile of new targeted nanoparticles will need to be carefully evaluated. Their group is now working on developing nanoparticle technologies that can be given orally and also ones that can penetrate the blood-brain barrier for treatment of brain metastases. The pioneering nanotechnology research initiated by Farokhzad and his team has led to the formation of several commercial enterprises, including BIND Therapeutics, Selecta Biosciences, and Blend Therapeutics. “Each one of these is advancing different types of nanotechnology towards evaluation in human clinical trials,” he says. Farokhzad predicts that “targeted nanoparticles are likely to be a very important contribution to the arsenal of cancer fighting drugs."
Research detailed in this article was funded in part by NIH grants, including K08EB003647 and R01EB015419.
— Emma Nichols