This document discusses opportunities for targeted cancer therapies using nanotechnology. It describes how nanoparticles can provide multi-functional capabilities like targeting, delivering, and reporting on drugs directly to tumor sites. This allows improved drug delivery with lower toxic side effects. The document outlines the National Cancer Institute's strategy to accelerate nanotechnology for cancer through centers of excellence, a nanotechnology characterization laboratory, and interagency collaborations on areas like characterization, standards, and training. It also discusses challenges in translating early-stage nanoparticle research into clinical studies and the need for public-private partnerships.

1. Cancer Nanotechnology:
New Opportunities for
Targeted Therapies
FDA Public Meeting
October 10, 2006
Piotr Grodzinski, Ph.D.
Director, Nanotechnology for Cancer Programs
Office of Technology and Industrial Relations
National Cancer Institute

2. • Provides multi-functionality: targeting,
delivery, reporting
• Provides improved therapeutic index
• Provides lowered toxic side effects
• Delivers multiple drugs directly to tumor site
• Enables nucleic acid delivery
• Enables non-drug therapies (photothermal,
photodynamic)
Nanotechnology-based Drug Delivery:
Key Benefits
Nanomaterial characterization: Responsible, Systematic, Standardized

3. Multi-Functional Nanoparticle-based Therapies
• Multi-functional platforms:
• Targeting
• Delivery
• Reporting, biosensing
In one package
Free drug formulations do not
possess multi-functional
characteristics
First generation of nano-delivered
drugs (no targeting) approved by
FDA – Abraxane®
M. Ferrari, Nature Reviews 5, 161 (2005)

4. Nanoshells:
Photothermal therapy
N. Halas, J. West et al,
Ann Biomed Eng. 34, 15 (2006)
Dendrimers:
Targeted delivery of methotrexate
Nanoparticle-based Therapies:
Different Approaches
J. Baker, et al., Cancer Res. 65, 5317
(2005)

5. Uncertainties of Moving Multi-Functional
Nanoparticles to the Clinic
• Differences exist between the development and regulatory pathway
for multi-functional nanoparticles and “traditional” drugs and
devices. Need to:
• Define the classification (decision tree) in order to determine the
characterization process ahead of the submission
• Provide interfaces within the regulatory agencies
• Establish uniform, publicly available guidelines for the investigators
• Determination if therapy is new when it uses an existing drug on a
novel delivery platform is a challenge
• Gap exists between technology development in an academic setting
and further technology maturation through clinical development and
regulatory approval

6. NCI Strategy:
Alliance for Nanotechnology in Cancer
A comprehensive, systematized initiative encompassing the public and
private sectors, designed to accelerate the use of the best capabilities
of nanotechnology to cancer applications
• Centers of Cancer Nanotechnology Excellence (CCNEs) and
Cancer Nanotechnology Platform Partnerships (CNPPs)
• To develop novel technologies to deliver drugs more effectively
• To develop new, highly sensitive and specific diagnostic techniques
• Nanotechnology Characterization Laboratory (NCL)
• To develop a standardized assay cascade for preclinical characterization
• To identify physical parameters and structure-activity relationships for
biocompatibility
• Not to address animal efficacy, SAR, PK or PD studies, or manufacturing

7. Next step
Adapted from Challenge and Opportunity on
the Critical Path to New Medical Products
(http://www.fda.gov/oc/initiatives/criticalpath/
whitepaper.html)
Nanoparticle Translation Mechanism:
From Early Development to the Clinic
Opportunities:
• Leverage NCL
capabilities
• Scale up the material
manufacturing (GMP)
• Provide studies towards
IND filing
• Initiate Phase 0/Phase I
trials
Challenges:
• High cost
• Low interest in academic environment,
where most of the innovation resides
• Partnerships with the industry needed
Nanotechnology
Alliance, NCL

8. Nanotechnology:
Environmental and Safety Considerations
• Hazard identification
• In vitro toxicity
• Acute in vivo toxicity
• Subchronic/chronic toxicity
• Route of exposure
• Dose response
• External dose
• Internal dose
• Biologically effective dose
• Exposure assessment
• Human exposure
Nanomaterials
production
Chronic exposure
of the worker
Nanomaterials
use for
biomedical
applications
Preclinical studies

9. Interagency Collaborations
• Characterization
• Critical path
development
• Training
• Public Interface
• Interpret Data
on Environment,
Health and
Safety
• Shared Data
and Platforms
• Standards/Precision
Measurement Capabilities
• Nanobiotechnology
Training

10. Interagency Collaborations
• Characterization
• Critical path
development
• Training
• Public Interface
• Interpret Data
on Environment,
Health and
Safety
• Shared Data
and Platforms
• Standards/Precision
Measurement Capabilities
• Nanobiotechnology
Training