National Cancer Institute

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National Cancer Institute
Dedicated to discovery aimed at the eradication
of cancer
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Where would we like to be?
Detection and Diagnosis
Malignant Tumors With Metastases
Year 0 Year 3 Year 6
Year 10
Prevention
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NCI Initiatives in Nanotechnology

• Mechanical/Sensors
• Cantilever, Nanowires, AFM, CNT
• Biological
• Nanoshells, nanoparticles, quantum dots
• Molecular Analysis/Diagnostics
• Structure, size, orientation, sequence
• Functional
• Detection, contrast enhancement, treatment,
  monitoring
• Smaller enables operations on the molecular
  scale.
• Less power, more sensitivity, parallel tests
• In vivo, detection to treatment, non-intrusive,
  one visit

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Quantum Dot
Quantum Dots can be transferred to water and
functionalized with Specific affinity molecules.

• DNA-DNA, Protein-Protein, DNA-Protein
• interactions can be studied on one platform
• No molecular label required
• Direct color-based visual readout

AFM/CNT

• single molecule detection enables both SNPs and
  haplotypes to be determined.
• high-resolution analysis of 100-1000 kb in single
  shot.
• no sample amplification required.

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Example of a Nanoparticle
Single Dendrimer Agent (5.0nm in diameter)
Dendrimer Cluster Agent (approx. 18 nm in
diameter)
Target Director
Contrast Agent
SensingFluorochrome Module
SensingFluorochrome
Contrast Module
Target Director Module
Therapeutic
Trigger Mechanism/ Nanocomposite
Interior-carried Therapeutic or Nanocomposite

• Target to tumor
• Imaging Capability to document presence of tumor
• Therapeutic agent delivered
• Documents response to therapeutic
• Identifies residual tumor cells

Light-activated Therapeutic
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Nanotechnology Benefit

• Diagnostics
• Real time, at home, disposable
• Early warning
• More sensitive (measure subtle changes)
• Less sample required
• Less sample preparation (no PCR, no
  amplification)
• Rapid screening
• thousands of molecules in drop of blood
• thousands of drug candidates at once
• In parallel
• 1 person all diseases
• 1 disease, 1000 people
• 1 disease, 1000 drug candidates
• 1000s of genes/proteins sequenced

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Patient Benefit

• Real time diagnosis
• Real time patient care, treatment, and
• monitoring response to treatment
• Minimizes invasiveness and pain
• Minimizes multiple visits
• Cancer detection at its earliest stages
• Potential to end chemotherapy and
• radiation treatment as we know it today

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Nano Science and NanoTechnologies NIH
priorities for 2002
NNanomaterials nano materials science to
interface with living tissues, passive delivery
of pharmaceuticals, enable tissue engineering,
and for contrast and biologically active
agents. NNano-imaging real-time intracellular
imaging of structure, function and
metabolism. Cell biology nano-scale research
of cellular processes, including biophysics of
molecular assemblies, membranes, organelles, and
macromolecules. Molecular and Cellular
Sensing/Signaling technologies to detect
biological signals and single molecules within
and outside cells. Nano-motors understanding
fundamental principles of nanomotor structure,
function, design and self-assembly.
Prosthetics mechanical, chemical, and
cellular implant nanotechnologies to achieve
functional replacement tissue architectures.
(Active components that replace a biological
function, e.g., actuation). Nano-Bio Processor
an implantable nano equivalent of a
microprocessor capable of controlling genetic,
biological and metabolic processes. Possible
applications include health status monitor,
prosthetic control, drug delivery control and
status, information extraction and reporting to
external source/physician, and electrical
stimulation for neural system, etc. Nanosystem
Design and Application fundamental principles
and tools to measure and image the biological
processes of health and disease, and methods to
assemble functional nanosystems. This could also
be tools to design nanosystems.
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National Nanotechnology Investment in the FY2003
Budget Request by the President
DoD DARPA nanostructures in biology info,
Chem/Bio sensors USAF nanocomposites,
nanoprocessing, nanoenergetics, nanoelectronics,
nanophotonics USA nanomaterials for soldier
protection DOJ -Wearable Chem/Bio sensors -Chip
based or microdevice technologies to analyze DNA
in forensic applications DOT -Sensors to detect
explosives hazardous chemicals including
chem/bio weapons (a/p chkpt) EPA -Sensors for
environmental monitoring, and food
safety USDA -New materials (textiles and
polymers) -DNA enzyme interactions, single
molecule interactions -Biosensors sensing
systems DOE -Facilities for synthesis,
processing, fabriaction, and analysis of
materials at nanoscale -Computational tools for
nanoscale science -Sensors
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National Nanotechnology Investment in the FY2003
Budget Request by the President
NASA -Materials and structures -Nanoelectronics
and computing -Sensors spacecraft components
NIH -Sensors tools for understanding at
molecular level cellular level -Detection,
treatment, monitoring of disease NIST -Nanomateri
als -Nanocharacterization (standards
tools) -Information technology, replacing
semiconductors NSF -Electronics,
optoelectronics -Biology -Advanced materials
engineering -Education -Nanoscale manufacturing
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National Nanotechnology Investment in the FY2003
Budget Request by the President
-Sensors (Chem/Bio/Explosives, Environmental,
Health, Molecular) -Materials (Composites,
Polymers, Magnetics, Photonics,
Electronics) -Fabrication (Tools, Standards,
Process)
Structure future efforts to minimize redundancy,
and maximize the expertise of the government
agency
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NIH Funding Mechanisms
Research Projects -P01 Integrated, Multiproject
Research -R01-R37 Research -R41-R44 SBIR/STTR
-U01-U44 Cooperative Agreement -P20-P50 Centers
Research Training Opportunities -T32-T35
Institutional Research Training -F31-F33 Individ
ual Fellowships -K01-K30 Career Development
Programs Contracts
Most announcements are open to all (university,
small/large business, government agency)
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Decision Tree to Determine Technology Maturation
End Goals
Is commercialization the end goal?
no
yes

• Possible End Goals
• Disseminate information to public
• domain
• Research tool/know-how for
• the community

• Possible End Goals
• License technology
• Technology/IP exchange
• Partnership
• Start a business

Is the technology aimed at clinical applications?
no
yes

• Possible End Goals
• Bench Research tool

• Possible End Goals
• Clinical research tool
• Clinical medical product

If successful, where can the results make the
greatest impact.?
FDA approval (animal trials, Human trials)
What metrics to evaluate whether my goal is still
appropriate?
Determine what kind of collaborator I need?
Require resources from NCI, state, or university?
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Commercialization Assistance Program (CAP)

• Program offered by Agencies
• individuals and companies to which they have
  provided RD funding
• No cost to program participant for services
• Participants invest considerable time
• Must participate in 1-3 events
• Objective - Increase likelihood of
  commercializing technology obtaining private
  sector funding partnerships
• Develop business plan, presentation materials
• Culminates in investor /partnering event

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Process for assisting companies

• Assigned to a portfolio manager
• Highly experienced individual
• Provides guidance, feedback, preliminary market
  research
• Business Planning for Scientists Engineers -
  text used as guide
• Highly interactive program
• Interact around selected activities called
  Interim Reports
• E-mail, phone

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Overview of CAP

• Outreach
• Kick-Off
• Interactive Business
• Planning (5)
• Biz Plan Critique
• Recommendation Selection
• Advanced Commercialization Workshop
• Plan Revisions Presentation Materials
• Investor Outreach
• Presentation
• Workshop
• Forum
• Follow-Up

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Multidisciplinary

• Curriculum
• Research
• Centers

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Summary

• Life Sciences Focus
• Provided a list of NIH priorities
• Analysis and Functionality on the Molecular Scale
  
• Provided a high level summary based on
  Presidential Budget
• Materials, Sensors, Fabrication
• How to Accelerate the Transition of Science to
  Application
• Combination of Grants and Contracts
• Universities, small/large business, government
  agencies
• Multidisciplinary support
• Get the researcher thinking commercialization
  early (e.g. CAP)
• How Should They Compete for Funding
• Task each government agency with a focus area
  that maximizes their expertise and limits
  redundancy
• Use the funding mechanism that is native to that
  agency

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BACKUP
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The Genetic Basis of Cancer

• Cancer results from the gradual accumulation of
  multiple genetic changes in single cells

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Cancerous cells undergo a gradual transformation
and often go undetected for years
Detection and Diagnosis
Malignant Tumors With Metastases
Year 0 Year 3 Year 6
Year 10
Therapy
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Innovative Molecular Analysis Technologies Program
Creating the Toolkit to Enable Molecular
Discovery and Speed Cancer Research

• Technologies suitable for in vitro, in situ, in
  vivo,
• and in silico analysis of
• alterations and instabilities in genomic DNA
• expression of genes and gene products
• cellular localization, post-translational
  modification,
• and function of proteins and
• monitoring major signal transduction networks
• involved in cancer

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Phased Innovation Awards

• Single submission and evaluation of both the R21
  and the R33 as one application, including
• R21 phase including measurable milestiones
• R33 phase including a credible development plan
• Flexible staging of feasibility and development
  phases
• R21 phase up to 2 years
• R33 phase 1 to 3 years
• 4 year maximum
• Parallel solicitation utilizing the SBIR and STTR
  mechanisms for small business
• Three receipt dates a year March, July, November

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Nanomechanical Biosensors for High-Throughput
Molecular Analysis
Quantitative Detection of PSA
200 mm Long, 0.5 mm Thick Silicon Nitride
Cantilever

• Guanghua Wu, Arun Majumdar
• (Mechanical Engineering, UC Berkeley)
• Karolyn Hansen, Hifeng Ji, Thomas Thundat
• (Biophysics, Oak Ridge Natl. Lab.)
• Ram Datar, Richard Cote (Cancer Pathology,
• U. Southern Cal.)

Supported by NCI Innovative Technology Program
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Nanowire Nanosensors

• Binding of chemical or biological species to the
  surface of a nanowire will result in depletion or
  accumulation of carriers.
• The change in carrier concentration due to
  binding can be directly monitored by measuring
  the nanowire conductance.

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DNA Analysis with Nanotube Probes Charles Lieber
Harvard University

• single molecule detection enables both SNPs and
  haplotypes to be determined.
• high-resolution analysis of 100-1000 kb in single
  shot.
• no sample amplification required.

Woolley Lieber, Nature Biotech (2000) Hahm
Lieber, submitted PNAS (2002)
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QUANTUM DOTS A NOVEL LUMINESCENT LABEL FOR
CELLULAR IMAGING
Homogenous, highly crystalline Material with
extraordinary optical Properties.
They can be transferred to water and
functionalized with Specific affinity molecules.
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LABELING OF SPECIFIC BREAST CANCER MARKERS WITH
CONJUGATED NANOCRYSTALS
Antigen/ Cell Type Label
P53 -535nm Sav- SKBR3 cells nanocrystal
Estrogen receptor - 535nm Sav- MCF7
cells nanocrystal
Her2 -630nm Sav- Breast cancer nanocrystal Tiss
ue section
Hugh Daniels Quantum Dot Corporation
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Unconventional Innovations ProgramTechnical Goal

• Technology platforms integrating
• non-invasive sensing of molecular alterations in
  vivo
• transmission of information to an external
  monitor
• controlled intervention specific for the
  molecular profile
• monitoring of intervention

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This contract targets the development of advanced
nanoparticles (10 to 100 nm) that link the
functions of detection and therapeutics.
Specifically, targeted MRI, optical imaging, and
photodynamic therapy will be supported by the
same dynamic nano-platforms (DNP) nanoparticles
with conserved cores. Activities will focus on
making and implementing conserved, multipurpose
systems, using novel concepts of hybrid chemical
materials, to make DNP that combine several
functions. These functions will include multiple
targeting, magnetic contrast, luminescence, and
photodynamic therapy through direct massive
delivery of reactive oxygen species. .
UNIVERSITY OF MICHIGAN Raoul Kopelman, Ph.D.