Themed issue on Cancer Nanotechnology

Abstract

Piotr Grodzinski

Dr Piotr Grodzinski is a Director of NCI Alliance for Nanotechnology in Cancer at the National Cancer Institute in Bethesda, Maryland. He coordinates program and research activities of the Alliance which has dedicated around $150M over a funding period of 5 years to form interdisciplinary centers as well as fund individual research and training programs targeting nanotechnology solutions for improved prevention, detection, and therapy of cancer. Dr Grodzinski is a materials scientist by training, but like many others found bio- and nanotechnology fascinating. In the mid-nineties, he left the world of semiconductor research and built a large microfluidics program at Motorola Corporate R&D in Arizona. The group made important contributions to the development of integrated microfluidics for genetic sample preparation with its work being featured in Highlights of Chemical Engineering News and Nature reviews. After his tenure at Motorola, Dr Grodzinski was with the Bioscience Division of Los Alamos National Laboratory where he served as a Group Leader and an interim Chief Scientist for the DOE Center for Integrated Nanotechnologies (CINT). At the National Institutes of Health (NIH), in addition to his programmatic responsibilities, he co-chaired the Trans-NIH Nanotechnology Task Force, which is coordinating the nanotechnology efforts across 27 institutes of the agency with the budget over $300M/year. Dr Grodzinski received a PhD in Materials Science from the University of Southern California, Los Angeles in 1992. He is an inventor on 15 patents and has published over 50 peer-reviewed papers, 7 book chapters, and delivered over 100 invited conference presentations. Dr Grodzinski has been an invited speaker and served on the committees of numerous bio- and nano-MEMS conferences in the past years.

Cancer is arguably the most complex disease known to man; it is also one of the most critical contemporary public health concerns. In 2010, the disease claimed close to 570 000 lives in the United States alone, while over 1.5 million Americans were diagnosed with cancer in that year. By 2020, the death rate is expected to reach over 10 million per year worldwide with costs to the healthcare system being already at $900 billion per year. Despite ongoing research and clinical efforts, the overall cancer treatment strategy has not changed significantly over the past 30 years and relies on the surgical resection of the tumor, followed by chemotherapy and/or radiation. There is some good news, though—numbers of cancer survivors are growing and increased from 3 million in 1971 to over 10 million today.

Recently, cancer biologists and clinical oncologists have been exploring nanomaterials and nanotechnology-based devices with hope to find more effective approaches to diagnose and treat cancer. Nanomaterials can enable targeted delivery of imaging agents and therapeutics to cancerous tissue, while nanoscale devices allow for multiplexed sensing to detect the disease early and monitor the effectiveness of the therapy. These advances are occurring due to the convergence of several disciplines ranging from materials science and physics to cancer biology and clinical practice. Intense research in the area of nanomaterials produced a diversified portfolio of nanoparticles which can be engineered to a precise size and shape using polymers, metals, lipids, and carbon. Nanoparticles combined with small molecule drugs are becoming powerful vehicles for localized drug delivery with improved efficacy and reduced side effects. A handful of nanoparticle-based formulations utilizing existing chemotherapeutics have already been approved by the FDA, several more sophisticated constructs involving active targeting and combination therapies are entering clinical trials. But, opportunities do not stop there, nanoparticles can also be used to broaden the therapeutic index of drugs which have been too toxic to be delivered in free format and ‘resurrect’ them for safe delivery.

Early detection improves cancer outcomes and the disease can be often cured when diagnosed in its primary stage before metastatic spread occurs. Cancer nanotechnology can improve these detection capabilities, through in vivo imaging contrast enhancement and in vitro device development. Magnetic resonance imaging, ultrasound, positron emission tomography (PET) will all benefit from the development of such nanoparticle-based contrast agents. Stratification of the patients based on this diagnostic information will lead to ‘precision medicine’ with an improved therapeutic efficacy for a given treatment, as compared to using this treatment in a broader population set.

New nanotechnology devices and constructs will soon become indispensable as tools supporting novel ways of diagnosing and treating the disease. However, nanotechnology is likely to play a significant role, which one might argue is even more relevant than producing positive clinical outcomes, in enhancing understanding of the fundamentals of cancer biology. For example, studies of single cell motion performed in vitro on specially nano-engineered surfaces are leading to new knowledge on cell migration and cell motility and may shed light on the mechanisms behind metastasis and result in the development of anti-metastatic drugs. Multi-drug resistance (MDR) mechanisms associated with cell-surface protein pumps can be studied and overcome using endocytosis mediated nanoparticle drug delivery. Nanoparticle constructs can also be designed to probe and recognize the tumor microenvironment via enzymatic, pH or other biochemical signaling allowing for bio-inspired imaging and the collection of additional information about the tumor as compared to traditional imaging modalities. Similarly, exposure of nanoparticle constructs to this microenvironment can allow for triggered and controlled drug release. Finally, multi-parameter analysis of genomic and proteomic signatures studied using diagnostic nano-devices will allow for the identification of biomarker sets responsible for the occurrence and progression of the disease. It is expected that newly produced knowledge on previously poorly understood mechanisms will empower the development of new and better treatments, which will hopefully relegate to medical history contemporary chemotherapy which is non-specific and toxic.

This themed issue of Integrative Biology focused on cancer nanotechnology presents a collection of several manuscripts, which were carefully selected in the spirit of demonstrating a power of inter-disciplinary research enabling characterization and understanding of biological systems with the subsequent aim of producing practical clinical outcomes.

Piotr Grodzinski, PhD

National Cancer Institute

October 2012

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