DEVELOPMENT AND APPLICATION OF NANOSCIENCE AND NANOTECHNOLOGY TO HEART, LUNG, 
AND BLOOD DISEASES, AND SLEEP DISORDERS 

RELEASE DATE:  December 4, 2002 
 
NOTICE: NOT-HL-03-005

National Heart, Lung, and Blood Institute (NHLBI) 
 (http://www.nhlbi.nih.gov/) 

Response Due Date: January 24, 2003

PURPOSE
 
The NHLBI is soliciting comments and ideas on approaches to develop and apply 
nanotechnology and nanoscience to the study, diagnosis, treatment, and 
prevention of cardiovascular, pulmonary, blood, and sleep disorders. 

BACKGROUND 

Nanoscience and nanotechnology are rapidly growing fields with significant 
potential to provide a new generation of scientific and technological approaches 
and of research and clinical tools and devices.  The essence of nanoscience and 
nanotechnology is the creation and use of molecules, molecular assemblies, 
materials, and devices in the range of 1-100 nm, and the exploitation of the 
unique properties and phenomena of matter at this dimensional scale.  
Nanotechnology comprises both top-down and bottom-up fabrication methodologies.  
In the former, nanoscale devices and their components draw inspiration from 
larger, currently known devices and components, while the latter pertains to the 
assembly of devices from individual atoms, molecules, and supramolecular 
structures of biological and synthetic origins.

In terms of heart, lung, blood, and sleep disorders, diagnostics, therapeutics, 
and biosensors are likely to be among the earliest applications of 
nanotechnology to become clinically important.  Furthermore, the use of 
nanoparticles opens new opportunities for localized targeting and controlled 
release of drugs and gene delivery.  Nanotechnology also provides new approaches 
for noninvasive molecular imaging, which may lead to advances in understanding 
the mechanisms of health and disease.  An additional area is the use of 
nanotechnology to develop biomimetic materials for use in tissue engineering.

An overarching vision that may be enabled by nanotechnology includes the 
development of systems that comprise intelligently linked diagnostics and 
therapeutic functions on a single, implanted or injected, multifunctional 
device.  While the individual functional components of such a device would be on 
a nanoscale, the entire device itself might be larger.  In this context, 
nanotechnology may provide innovative solutions to the problem of in-vivo 
targeting.  Of interest is the development of 'smart' systems for the release of 
therapeutic agents, where 'smart' refers to any combination of the following 
capabilities, in surgically implanted, injected, inhaled, and orally, or 
otherwise administered devices:  

o   Concentration of therapeutic action exclusively or predominantly at a 
desired target site;
o   Avoidance of biological and biophysical barriers to the penetration and 
efficacy of the therapeutic action;
o   Release of therapeutic action in desired, pre-programmed time-dependent 
patterns;
o   Operator-controlled, remotely activated release of a therapeutic agent.  In 
a scenario of interest, the in-vivo nanodevice  would sense and relay 
information to the attending medical personnel, who would then regulate the 
release of a therapeutic agent;
o   Self-regulated release of therapeutic action, from a device comprising 
sensors of appropriate biomarkers, release technology, and on-board intelligence 
connecting these functions.

Some examples of specific, broad areas of interest for application of 
nanotechnology include clinical scenarios involving inflammatory processes, 
fibrosis, and tissue damage and repair.  However, interest is not limited to 
these areas only.  Systems that may provide the above-listed combination of 
nanotechnology-enabled functionalities include:

o   Molecular assemblies or particulates for diagnostic imaging (smart contrast 
agents) and targeted therapeutics;
o   Molecular assemblies capable of targeted release;
o   Implantable systems for controlled actions, including drug release chips and 
stents;
o   Substrates and templates for organ and/or tissue repair;
o   Circulating or implantable hybrids comprising biological cells and synthetic 
elements for tracking, imaging and therapeutics;
o   In-vivo assessments, including mechano-chemical sensing technology;
o   Molecular assemblies that can be addressed externally by application of a 
magnetic or electrical field, sound waves, radiation, etc.

INFORMATION REQUESTED 

The NHLBI seeks your help in identifying (a) the major opportunities in 
developing and applying nanoscience and nanotechnology to heart, lung, blood, 
and sleep research and medicine; (b) the critical needs to enable progress and 
the barriers that may inhibit it; and (c) practical and effective ways to meet 
the needs, overcome the barriers, and take full advantage of the opportunities. 
Your thoughts, ideas, and suggestions will be used to help guide future 
Institute activities designed to expedite the development and application of 
nanoscience and nanotechnology to biological research questions and efforts to 
improve patient care. Respondents are asked to comment on one or more of the 
issues listed below, but should not feel compelled to address all of them.

1.   Please comment on what you view as the major opportunities for developing 
and applying nanotechnology and nanoscience to heart, lung, blood, and sleep 
research and medicine.  Please suggest areas that are particularly promising and 
are of highest priority. 

2.   Please identify the major needs for and barriers to developing and applying 
nanotechnology and nanoscience to heart, lung, blood, and sleep research and 
medicine.

3.   Please suggest approaches the NHLBI can take to meet the needs, overcome 
the barriers, and take full advantage of the opportunities.  Any specific 
suggestions and general estimates of associated costs would be valuable. 

4.   Please consider and comment on regulatory issues that are likely to be 
encountered in applying nanotechnology to NHLBI-supported research (e.g., need 
for coincident approval for novel imaging agents with the corresponding 
instrumentation).  Please include ideas on how these issues can be overcome.

5.   Please provide other examples of nanoscience and nanotechnology, real or 
imaginary that might be suggested for application to heart, lung, blood, and 
sleep research and medicine.

6.   We would appreciate any additional views or opinions that you think would 
be useful.

RESPONSE AND PROCESS 

Responses in any of the areas are welcome; respondents should not feel compelled 
to address all items.  Please respond no later than January 24, 2003.  Responses 
will be compiled and shared with our advisory committees.  We look forward to 
your thoughts, opinions, and suggestions and hope you will share this document 
with your colleagues.  Thank you very much for your help. 

To respond, please link to the online form in the What's New section on the 
NHLBI Home Page (http://www.nhlbi.nih.gov/funding/inits/nanorfi.htm), or send a 
letter, fax, or e-mail to the following address: 

Tawanna Meadows
Two Rockledge Centre
6701 Rockledge Drive
Room 9163, MSC 7940
Bethesda, MD 20892-7940
Telephone: (301) 435-1802
FAX: (301) 480-1335
E-mail: NHLBINano@nhlbi.nih.gov

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