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Rice UniversityCBEN
Center for Biological and Environmental Nanotechnology
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Theme 2: Nanoparticles that Sense and Treat Disease

Our ever-improving understanding of the progression of most pathologies has come primarily from imaging and histology. However, it is molecular studies, generally at the subnanometer scale, that have elucidated many key biochemical pathways. Major advances in both diagnostics and therapeutics can be achieved by working at the length scale that bridges these domains—the nanoscale. Working at the nanom¬eter scale affords the opportunity to design inorganic materials with novel imaging, therapeutic, and delivery capabilities. At the same time, working at the nanoscale enables the engineering of new organic materials with novel biological recognition, sensing, transducing, and therapeutic functions. We have the ability to develop nanocomposites that can be designed to sense, target and manipulate biological activities with unprecedented sensitivity and spatial resolution by combining inorganic and organic nanomaterials. This vision motivates CBEN’s systems goal: “Nanoparticles that sense and treat disease,” and drives all Theme 2 projects.

  • Specific destruction of tumor cells including prostate, breast, brain and tumor vasculature cells through direct nanoshell targeting.Development of molecular beacons for functional gene expression imaging, leading to specific detection of human papillomavirus (HPV) ribonucleic acid (RNA) in living cells.
  • Development of smaller, more highly absorbing NIR nanoparticles and manufacturing techniques for
  • Improvement in photothermal tumor ablation therapy

Of particular interest to many of the Theme 2 projects in CBEN is the diagnosis and treatment of cancer. Cancer kills >25% of our population (American Cancer Society), and yet despite tremendous advances in our understanding of the molecular and cellular processes of cancer, there has been no change in the age-adjusted mortality due to cancer (Centers for Disease Control and Prevention [CDC]). Nano¬technology may offer new options for earlier and more accurate detection of cancer as well as more effective therapies; CBEN-funded projects have already shown considerable promise in both of these areas. Of particular note, nanoshell-assisted photothermal ablation (project 2.2.1) is currently in the midst of an FDA-approved phase I clinical trial for patients with recurrent and refractive head and neck tumors and an Investigational Device Exemption has been filed for a second phase I trial for patients with metastatic prostate cancer.  These clinical trials represent a collaborative effort between Rice, Nanospectra Biosciences, Inc. (founded by Theme 2 leader Jennifer West), and several hospitals.  These trials have been funded by the Texas Emerging Technologies Fund.  Dr. Drezek also has a clinical study ongoing to examine tumor margin detection in 20 HER2+ breast cancer patients using immunotargeted nanoshells.

Common to the majority of Theme 2 projects is a focus on biophotonics, particularly using materials that are active in the near infrared (NIR). Nanoscale materials provide interesting and unique optical properties that are ideal for many biological imaging applications. They can have bright and tunable fluorescence, tunable and controlled absorption and scattering, and activatable optical responses. In most cases, working with nanomaterials rather than dyes provides resistance to photobleaching as well. An additional property of nanoscale optical properties is the multitude of materials and optical responses that occur in the NIR, where transmission of light through tissue is maximal. Very few nontoxic NIR chromophores are available, so this is a unique and important capability of the proposed nanomaterials.

In addition, the Center continues its outreach and collaboration with the Food & Drug Administration (FDA). Clearing the FDA is a significant hurdle for CBEN projects aiming at the systems-level goal in bioengineering.  This year, the FDA formed a public-private partnership focused on lowering barriers to nanomaterial approval by the FDA. Hosted by the Alliance for Nanohealth, a multi-institution consortium in Houston, Rice, and CBEN will play integral roles in defining and implementing projects developed by this Critical Path Initiative.

CBEN has supported the development of a highly collaborative research environment related to biomedical applications of nanoparticles.  The large number of coauthored publications between Drezek and Colvin over the past two years and 2008 published work between Drezek  and Hafner attests to the success of this effort and to increasing Theme 1/Theme 2 and Theme 2/Theme 3 interactions while the multiple CBEN papers with high cita-tion counts between Drezek and West (including two papers with >200 citations each and several others with 50-100 citations) indicate the growing impact of CBEN Theme 2 collaborative work between Projects 9.2.2.1 (cancer therapy) and 9.2.1.1 (cancer imaging).  In 2009 Small named a joint Drezek and Colvin 2008 CBEN review paper as its most accessed article published in 2008, and in 2009 Scopus TopCited listed a joint West and Drezek NanoLetters 2005 CBEN paper as one of the top 10 most cited articles in material science over the past five years (2005-2009).

Further information on Theme 2 projects can be found in the CBEN Annual Reports.