Nanotechnologies for Biomedicine • Opportunities • Challenges • Implications for Technology Management and Innovation

OECD Workshop Travis M. EARLES Better Health through Biomedicine Assistant Director for Nanotechnology Innovative Governance Office of Science and Technology Policy Berlin, GERMANY EXECUTIVE OFFICE OF THE PRESIDENT 27-28 September 2010

1 What is Nanotechnology?

Scale – approximately 1-100 nanometers

Water Glucose Antibody Virus Bacteria Single Cell Human Hair

10-1 1 10 102 103 104 105 106

Nanometers

Control – engineering and manipulation of materials

Emergent properties – uniquely derived as a result of nanoscale control

2 Why Nanomedicine?

• Novel properties of nanomaterials

– Surface area to volume – Morphology, aspect ratio – Charge and conductance – Multifunctional and multiplexing capability

• Structures and devices functionalized directly and/or integrated into larger material components, architectures, and systems

– DNA sequencing – Single cell interrogation – Circulation profile management – Drug formulation and biomarker-based targeting – Tissue penetration

3 Impacts of Nanomedicine

Nanotechnology innovation and life sciences join to improve existing and develop new biomedical applications

• Detect disease conditions early, pre-symptomatically – Sensors – Imaging • Target therapeutics – Localize delivery – Monitor effects post treatment – Improve efficacy • Develop research tools to enhance understanding and enable study of biological functions and disease processes

4 Nano-based Diagnostics

• Multiple sample types – blood, serum, urine, or saliva • Sample handling – separate and/or components (e.g., circulating tumor cells) • Multiplexing – identify several molecular signatures simultaneously • Multifunctional – one platform capable of detecting nucleic acids and proteins DEAL (DNA Encoded Integrated BioBarCode RBC Antibody Library) IBBC WBC Currently tested Plasma (99% purity) for molecular and functional analysis of glioblastoma tumors

DEAL barcode Less than 10 min working Plasma protein 20 µM time DNA codes J. Heath Caltech – Nature Biotech (2008) 26: 1373 IBBC - microfluidic device for multiplexed detection of proteins in whole blood sample DEAL - ssDNA bound to antibodies that are labeled with complementary ssDNA

5 Nano-based Therapeutics

Targeted chemotherapy Hyperthermia Photothermal

J. Baker, et al., Cancer Res. (2005) 65 : 5317 N. Halas, J. West et al, Ann Biomed Eng (2006) 34:15

Encapsulated and targeted siRNA RF-heated

Liposome Magnetite nanoparticle

A. Ito et al., J. of Bioscience and Bioeng. (2005 100: 1) M. Davis et al. Nature (2010) 464: 1067

6 Nanoparticle Production – one approach

Particle Replication In Non-wetting Templates • soft lithographic imprint technique • < 50 nm precision • controlled structure (shape, size, composition) enables tuning of delivery • controlled functionalization (cargo, surface) enables protection, staged and/or

polymer sheet targeted delivery of therapeutics or precursor roller imaging agents solution mold solution Effects of size, shape and aspect ratio ROLLING excess on internalization • preferential cellular uptake of cylindrical NPs CURING in the mold

REMOVING from the mold

HARVESTING

J. DeSimone – UNC – PNAS (2008) 105: 11613 WIRES (2009) 1: 2917 Nanoparticle Characterization

The Nanotechnology Characterization Laboratory is a formal collaboration between the National Cancer Institute, the Food and Drug Administration and the National Institute of Standards and Technology.

8 Oversight Challenges Unique to Nanomedicine?

• Questions? Always. • Some technology-specific issues • Many challenges are not unique • Nanotechnology-induced “pinch-points” on regulatory frameworks – Exquisite compositional control – Material characterization and particle distribution – Multifunctionality • Common to other areas? Overarching issues – Progress of basic research and development to application – Balance of risk and benefit with limited knowledge, uncertainty – Engagement of stakeholders, building trust

9 Guiding Principles

• Count the opportunity cost • Balance risks and benefits • Distinguish bases of policymaking – Science – Economic – Ethical – Other • Adapt and modernize regulatory oversight – Identify emerging technological and validation challenges early – Assess efficiency, engagement, performance – Define and streamline pathways based on both scientific and policy challenges • Share data and best practices – Working Party on Nanotechnology survey of food and medical products

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