A $16-million, five-year grant by the National Cancer Institute’s nanomedicine initiative blends the expertise of five research institutions to focus an array of innovative nanotechnologies on improving the outcome of patients with ovarian or pancreatic cancers.
The Texas Center for Cancer Nanomedicine, an NCI Center for Nanotechnology Excellence funded by the grant assembles researchers from The University of Texas MD Anderson Cancer Center, The University of Texas Health Science Center at Houston (UTHealth), The Methodist Hospital Research Institute, Rice University and Albert Einstein College of Medicine In New York.
Team members have developed nanoparticles made from a variety of substances that hold potential for medical use, including gold, silicon, tiny balls of fat called nanoliposomes and chitosan, which is derived from crustacean shells. A nanometer is one billionth of a meter. Nanoparticles are engineered materials that are 100 nanometers or less in size – the scale where most biological functions occur.
The TCCN anticipates launching clinical trials of its nanomedicine therapies 24 months after the center opens. The grant from the NCI Alliance for Nanotechnology in Cancer will not fund the clinical trials.
“We believe our team of internationally recognized scientists will push the boundaries of cancer therapy and diagnosis, starting with two cancers that are among the hardest to detect and the most difficult to treat,” said Anil Sood, M.D., professor in MD Anderson’s departments of Gynecologic Oncology and Cancer Biology, one of four principal investigators.
Sood, David Gorenstein, Ph.D., deputy director of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth, Gabriel Lopez-Berestein, M.D., professor of Experimental Therapeutics at MD Anderson, and Mauro Ferrari, Ph.D., president and CEO of The Methodist Hospital Research Institute, are co-principal investigators of the center.
Ovarian cancer is the fourth-leading cause of cancer death among women. The NCI estimates 13,850 will die of the disease in 2010. Pancreatic cancer is the fifth-leading cause of cancer death, with 36,800 expected fatalities this year. There is no early detection strategy for either disease.
“Our understanding of the natural and physical barriers that impede development of drugs guides the advancement of our nanomedicine approaches for the prevention and personalized treatment of cancer,” said Lopez-Berestein, who pioneered the field of nanomedicine in 1995 with a version of the antifungal drug amphotericin B encapsulated in a liposomal nanoparticle.
- Gold nanoparticles for therapeutic and diagnostic use, Jennifer West, Ph.D., Rice University
- Hollow gold nanoparticles, Chun Li, Ph.D., MD Anderson
- Mesoporous silicon nanoparticles for multistage carriers and proteomic nanochips, Mauro Ferrari, Ph.D., Methodist Research Institute
- Thioaptamer constructs, David Gorenstein, Ph.D., UTHealth
- Neutral nanoliposomes, chitosan and rHDL nanoparticles, Anil Sood, M.D., and Gabriel Lopez-Berestein, M.D., MD Anderson
- Nanoassemblies and phage display, Renata Pasqualini, Ph.D., and Wadih Arap, M.D., Ph.D.
“This is a triumph of the multi-institutional collaborations fostered and developed over several years with the Alliance for NanoHealth in Houston,” said Ferrari, who is president of the alliance of Houston-area research institutions. “It’s the fifth large center we’ve been able to fund in the last four years. This unparalleled success speaks volumes about the primacy of Houston-area institutions in both cancer and nanotechnology, and our ability to work together.”
In addition to being accomplished developers of nanoparticles, the team also has expertise in research about and treatment of pancreatic and ovarian cancers, drug development, moving ideas from the lab to clinical trials (translational research), as well as entrepreneurial experience forming local spin-off companies and working with existing pharmaceutical and biotech companies to broadly distribute new therapies.
Center researchers have an extensive record of collaboration among themselves and strong connections to other nanotechnology experts.
“We know each other’s strengths, we understand each other’s roles, we trust each other, we’ve taken years to form the complete team that can bridge the laboratories to the clinic, and we’re unanimously focused on clinical translation,” said Gorenstein, who also is associate dean for research at the UTHealth Medical School.
Because all of the TCCN’s nanotechnologies are delivery platforms, the impact of the center’s research is likely to reach beyond cancer.
Center research is divided into four projects, with scientists from multiple institutions using a variety of nanoparticles in each.
- Multiple-stage delivery systems that can efficiently put drugs or small interfering RNA in ovarian cancers and the blood vessels that support them. This project also includes development of a sensitive imaging approach and proteomic nanochips to monitor response to treatment.
- Highly targeted therapeutic nanoparticles designed specifically to hit the blood vessels that support ovarian cancer tumors using novel thioaptamer and peptide targeting agents. Two nanotechnologies will be deployed – one that delivers siRNA to silence target genes and another that will permit the burning of blood vessels with near-infrared laser light.
- Nanoparticles that can penetrate or destroy connective tissues that are abundant in pancreatic cancer tumors and block destruction of cancerous cells. Three types of nanoparticles and two types of targeting agents will be used against the fibrous material. Nanoparticles also will be tested as preventive agents to reverse conditions that nurture cancer formation and as a method of early detection.
- Multifunctional nanoassemblies capable of treating neuroendocrine pancreatic tumors by homing in on a specific vascular address marking the blood vessels that feed the tumor and then delivering smaller nanoparticles to either treat or image the malignancy.
TCCN also includes four core programs that support the researchers with targeting expertise, biomathematics, nanoengineering and administration.
Jennifer West, Ph.D., professor and chair of Rice University’s Department of Bioengineering, Paolo Decuzzi, Ph.D., senior member and co-director of Methodist Research Institute’s Department of Nanomedicine, Craig Logsdon, Ph.D., professor in MD Anderson’s Department of Cancer Biology, and Wadih Arap, M.D., Ph.D. of MD Anderson’s David H. Koch Center serve as project or core leaders of the TCCN. Paolo Decuzzi (Methodist),
Investigators on this project are also affiliated with MD Anderson’s Center for RNA Interference and Non-Coding RNAs, the first such center in the United States, which is designed to foster multidisciplinary and multi-institutional collaboration.
Rahul Mitra, director of the molecular markers program in MD Anderson’s Department of Gynecologic Oncology, is director of the TCCN.