Do we need a reality check?
Cancer treatment has been a poster-child for nanotechnology for almost as long as I’ve been involved with the field. As far back as in 1999, a brochure on nanotechnology published by the US government described future “synthetic anti-body-like nanoscale drugs or devices that might seek out and destroy malignant cells wherever they might be in the body.”
Over the intervening decade, nanotechnology has become a cornerstone of the National Cancer Institute’s fight against cancer, and has featured prominently in the US government’s support for nanotechnology research and development. And for good reason – nanotechnology holds the promise of treatments that can diagnose cancer earlier in the disease’s development than ever before; treat tumors using lower concentrations of chemotherapy agents, and target malignant cells while leaving healthy cells untouched.
Like many of my colleagues, I have used emerging nanotechnology-based cancer treatments as a compelling example of what is possible when we gain mastery over materials at the scale of the atoms and molecules they are made of. So I was somewhat surprised to see the eminent chemist and nano-scientist George Whitesides questioning how much progress we’ve made in developing nanotechnology-based cancer treatments, in an article published in the Columbia Chronicle.
According to the article:
George Whitesides, professor of chemistry and chemical biology at Harvard University, said that while the technology sounds impressive, he thinks the focus should be on using nanoparticles in imaging and diagnosing, not treatment.
The problem lies in being able to deliver the treatment to the right cells, and Whitesides said this has proven difficult. “Cancer cells are abnormal cells, but they’re still us,” he said.
Whitesides went on to comment that:
“It’s easy to say that one is going to have a particle that’s going to recognize the tumor once it gets there and will do something that triggers the death of the cell, it’s just that we don’t know how to do either one of these parts.”
This got me thinking – because George is a smart guy and well worth paying attention to – have we somehow got so caught up in the possibilities of nanotechnology in treating cancer, that we have lost sight of the realities?
To get a better sense of where we are on nanotech-enabled approaches to treating cancer, I asked a handful of experts working in the field the following question:
What are some of the more significant science challenges researchers face in developing nanotechnology-based cancer treatments?
The responses were cautious, and clearly cognizant of the hurdles to taking scientific and technological breakthroughs out of the lab and into the market. Yet despite this, there was an over-riding sense of optimism running through them.
Steve Rosen, Director of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University commented:
“I feel nanotechnology has the possibility of revolutionizing both in vitro and in vivo cancer diagnostics. Therapy always remains a greater challenge and in the short term I see nanotechnology as a vehicle to enhanced delivery. The long term prospects are substantial and limited only by the creativity of individuals involve in this area of investigation.”
This was echoed by Tyler Jacks, Director, David H. Koch Institute for Integrative Cancer Research at MIT:
“Nanotechnology holds great promise for cancer therapy, in my view. That said, there is need for more research to learn the best strategies to specifically direct the nanomaterials to cancer cells following systemic administration. This will require overcoming the body’s natural filtration systems as well as optimizing the methods for tumor-specific targeting. It may be that truly tumor-specific targeting will require combinatorial approaches.”
The difficulties of overcoming biological barriers to using nanoparticles effectively in treating cancers were expanded on by Martin Philbert, Senior Associate Dean at School of Public Health, University of Michigan:
“The body’s immune system is primed to recognize particles of the size range encompassed by most therapeutic and imaging nanotechnologies. Since elements of the immune system are coordinated and disseminated throughout the body, a major challenge is the design and fabrication of nanotechnologies that will either avoid immune cells or use them to achieve appropriate targeting without activation or suppression of immune function.
“A second major hurdle is elimination from the body. Many of the newer nanoparticles are designed to be eliminated from the body by either being ’small’, i.e., less than 8 nm in diameter to facilitate passage with the urine out of the kidneys, or to dissolve to a size that allows for elimination through the urinary flow. Nevertheless, the kinetics of elimination are invariably altered by the ability of the reticuloendothelial portion of the immune system to take up these materials and sequester them in lymphatic organs or interstitial spaces for longer periods than anticipated.”
Yet despite the challenges, progress is clearly being made. Piotr Grodzinsky, Director, Nanotechnology Cancer Programs at the National Cancer Institute noted that:
“Nanotechnologies for medical applications have been maturing. Several therapeutic formulations entered clinical trials and are expected to have an impact on how cancer treatment is done in the future. Similarly, multiplex diagnostic platforms with high sensitivity and specificity are proving themselves in testing of clinical specimens and will contribute to early disease detection.”
Scott McNeil, Director of the Nanotechnology Characterization Laboratory cautioned that:
“Developers of nanotech-based therapeutics face preclinical challenges that may be more involved than development of small molecule drugs…”
But went on to add:
“…the payoffs are now being demonstrated in clinical trials by several companies. We are observing a consistent trend towards decreased toxicity for nanodrugs compared to their small molecule counterparts.”
And in responding specifically to Whitesides’ comments, Jim Baker, Director of the Michigan Nanotechnology Institute for Medicine and the Biological Sciences, observed that:
“[George Whitesides] is correct that this is a very complex problem, with cancer as a variation of self being a central issue. In addition, the concept of some in the material science community that nanoscale materials would be inherently better ignores potential problems related to biocompatibility and the necessity of this material to function in a wet environment. Additionally, the concept of a “nanomachine” is fundamentally flawed because having mechanical devices of this size violates the laws of physics. What is moving forward are bio-inspired materials that will provide incremental improvements in drug delivery and imaging that could not be accomplished with traditional materials. Each one will be unique, however, and require its own evaluation for efficacy and toxicity, just like any other drug. This provides a difficult hurdle, given the costs and clinical evaluations that are involved.”
Reading through these comments, I get the sense that we’re only beginning to scratch the surface of what working at the nanoscale can do for cancer treatment. Certainly there are hurdles to be overcome – some of them significant. And it’s important to remember that the road between lab-based discoveries and real-world treatments is a long and arduous one – even the most promising therapies can take years or even decades to get to the point where they are widely available.
Yet it’s hard to avoid being caught up in the enthusiasm of scientists working on nanotechnology-enabled cancer treatments, or not to be inspired by what might be achieved through engineering increasingly sophisticated therapeutics at the nanoscale.
That said, expectations on how nanotechnology will impact cancer treatment clearly need to be tempered. In this respect, I thought that the comments from Jennifer West, the Isabel C. Cameron Professor of Bioengineering at Rice University, were particularly well-grounded:
“Nanotechnology isn’t a magic solution to cancer, but provides additional tools in the arsenal, some with new and unique properties. As with any cancer therapy, the key issue is to get the therapeutic agent to tumor sites and metastases at high concentrations, then destroy cancerous cells while minimizing damage to normal cells.”
Nanotechnology is clearly not a panacea. It provides exciting new opportunities for treating cancer. But its use also faces many scientific, economic and regulatory hurdles.
Yet the idea of crafting more effective cancer treatments by engineering matter at the nanoscale remains a compelling one – if only we can work out how to translate the idea into practical solutions.
As one of my sources – who preferred not to be named – commented:
“I don’t think that the field needs a reality check but rather ways to move more of the discoveries and developments into humans.”