Opportunities in Cancer Nanotechnology: A Conversation with NCI’s Dr. Piotr Grodzinski
NCI recently released the Cancer Nanotechnology Plan 2015. In this interview, Piotr Grodzinski, Ph.D., director of NCI’s Office of Cancer Nanotechnology Research, discusses the 2015 plan as well as new developments in nanotechnology-based therapeutics and diagnostics and the clinical opportunities being generated by the nanotechnology field.
To begin, can you explain what nanotechnology and nanomedicine are?Sure. Nanotechnology is the science and research related to extremely small objects, usually in the range of 100 nanometers or so, that exhibit unique properties because of their small size.
Many nanotechnology-based devices have already found their way into medical applications, primarily in two major areas: one is therapeutics and drug delivery, and the other is diagnostics and detection.
A key advantage of nanoparticle-based therapeutics, or nanomedicines, is that they can be delivered to tumors in a more localized fashion than traditional drugs—such that these therapies should have fewer side effects and potentially better efficacy.
That’s because compared to “free-drug” delivery, nanoparticle-based therapeutics circulate in blood for longer following systemic injection and allow for delayed drug release after the construct reaches the tumor. Nanoparticle-based drug delivery may also allow medicines to cross physiological barriers that normally tend to impede delivery. For example, researchers are developing nanoparticles that may be able to more effectively penetrate the thick stroma that tends to surround pancreatic tumors and nanoparticles that can cross the blood-brain barrier to improve systemic treatment of brain cancer.
There are also other nanoparticle-based therapies that don’t carry drugs but work in other ways. For example, nanoparticles that traffic to tumors can be heated by interaction with external radio frequency fields or near-infrared light to generate hyperthermia and kill tumor cells. Elevated temperatures may also increase the efficacy of other treatments. For example, this approach can help to increase uptake of other particles or small-molecule drugs, or it can be used in synergy with radiotherapy.
In terms of diagnostics, new nanotechnology-based devices may allow oncologists to simultaneously monitor many different biological signatures of cancer present in blood or other bodily fluids, whether they are proteins, DNA, circulating tumor cells, or metabolites.
Are any nanomedicines currently in use?The Food and Drug Administration (FDA) has approved a handful of drugs that rely on nanoparticle-based delivery, with DOXIL®, a liposomal formulation of doxorubicin, and Abraxane®, an albumin-stabilized nanoparticle formulation of paclitaxel, being the most widely used. The former was initially approved for Kaposi sarcoma and the latter for metastatic breast cancer, but since their initial approvals they have also been tested and approved for the treatment of other solid tumors.
Most recently, Onivyde™, a liposomal formulation of irinotecan was approved for the treatment of pancreatic cancer.
Nanomedicine designs currently in clinical trials include targeted therapies using nanoparticles equipped with ligands (binding molecules), which selectively identify tumor cells, and combination therapies, which allow for leveraging of synergistic effects of several drugs delivered at the same time.
What are NCI’s major nanotechnology-related initiatives?About 10 years ago, NCI launched a large funding initiative called the NCI Alliance for Nanotechnology in Cancer, to support academic groups dedicated to research on nanotechnology for cancer applications. At that time, NCI recognized that this kind of research would require a multidisciplinary approach, since many innovative nanotechnologies are developed by researchers in physics, engineering, and chemistry, while, of course, the medical applications need to be driven by cancer biologists and oncologists.
In 2004, NCI also established the Centers of Cancer Nanotechnology Excellence (CCNE), which fund multidisciplinary teams with special expertise in nanotechnology at institutions across the country.
The focus of these centers is translational—that is, the funded research is expected to lead to practical cancer interventions with strong clinical potential. To facilitate clinical translation, the centers are expected to build relationships with private-sector companies. Several start-up companies have already been formed as spin-offs from NCI-funded CCNEs. These start-ups are involved in several clinical trials testing nanotechnology-based therapeutics and diagnostics.
The Alliance also formed an intramural lab, the Nanotechnology Characterization Laboratory (NCL), operated by Leidos Biomedical, in Frederick, MD. The NCL’s efforts are dedicated to assessing novel nanomaterials and their utility in cancer therapeutic applications. The NCL works with numerous academic and industrial entities across the world.
Your office recently published the Cancer Nanotechnology Plan 2015. What is included in the plan?We develop a strategic plan at the beginning of each 5-year program phase. The purpose of this plan is to chart strategic directions for the field of cancer nanotechnology and make it available to the research and commercial communities for use as a guide to identify areas that they may want to pursue.
The plan is developed in close collaboration with the extramural research community, with leading researchers contributing chapters related to their areas of expertise. In the latest plan, we outline some of the more mature concepts that are ready to be tested in clinical trials. We also highlight emerging new areas of research.
Can you talk about some of those emerging areas?One important emerging area is related to repurposing drugs that are too toxic to be delivered in their free form. Packaging these drugs into nanoparticles can potentially reduce their toxicity and open the therapeutic window so we can take advantage of the true potency of these drugs. We are currently working with the NCI Division of Cancer Treatment and Diagnosis on a pilot program dedicated to this area.
Another opportunity is to use nanoparticles in the burgeoning area of cancer immunotherapies. For instance, it may be possible to use nanoparticles to deliver drugs that stimulate the immune system or even to serve as artificial antigen-presenting cells.
Nanoparticles are also being studied as tools for monitoring the surgical removal of tumors in real time. They can be used to demarcate tumor margins, allowing them to be visualized to improve surgical accuracy.
We are also exploring new avenues of nanoparticle delivery. Most nanoparticles right now are delivered directly into the tumor or systemically through an intravenous line, like most chemotherapies. The question is whether nanoparticles can also be delivered orally or inhaled, which are less invasive and more comfortable for the patient.
Finally, the plan also highlights the idea of “liquid biopsies”: using nanoparticles or nanodevices to analyze blood samples from cancer patients to search for rare circulating tumor cells or circulating tumor DNA. These approaches are being tested as both early diagnostic tools and as a way to monitor the effectiveness of therapy.
What is NCI’s role in the Nanotechnology Startup Challenge in Cancer?Nanotechnologies developed in academic laboratories are typically translated to clinical use by small companies that have spun off from academic labs, rather than by large pharmaceutical and biotechnology companies. Forming these startup companies is not always easy; the key is to find the right investors. There is a growing interest among investigators to seek alternate ways of forming and financing these companies.
The goal of a startup challenge is to identify intellectual property—patents—developed by NIH intramural investigators that are being made available for commercial development. Interested parties can then develop short business plans focused on commercialization of the technologies covered by these patents. The CAI then solicits skilled judges from industry and academia to assess the business plans, and eventually a few of the plans float to the top. The winning groups then work with CAI and prospective investors to form a company.
The Nanotechnology Startup Challenge in CancerExit Disclaimer is another iteration of this initiative. We are soliciting business plans to commercialize patents from intramural NCI investigators and even NCI-supported extramural investigators. We hope that the challenge will aid the formation of new startup companies.
So, as you can see, our general approach with nanotechnology is to balance promoting new discoveries originating from academia with strategies for translating them into clinical practice.
Overall, our goal is to capitalize on the potential of cancer nanotechnology by developing and commercializing nanotechnology-based treatments and diagnostic tools and bringing them into mainstream cancer care. Without effective translation from the lab to the clinic, the field will continue to be a curiosity rather than something that is providing solutions for patients.