Smart, Nano-sized “vulnerable plaque” Detectors
Level - GradSudden death due to heart attacks continues to be the leading cause of sudden death in Western countries and thus the most serious challenge to doctors and patients. Striking relatively young and seemingly healthy men and women in their 40’s and 50’s, these sudden heart attacks generally occur when “vulnerable or unstable” atherosclerotic plaques rupture unexpectedly blocking the blood supply to the heart. In many cases, doctors and patients often say that the patient was thoroughly examined only 3 or 4 weeks prior to the attack and showed no signs of impending plaque rupture. There is a critical need for detecting the “vulnerable plaques” before they claim many more lives.
To respond to this urgent and critical need, the NIH has released the following announcement (see the attached NOTICE: NOT-HL-03-005, http://grants2.nih.gov/grants/guide/notice-files/NOT-HL-03-005.html) and the brilliant teams of BME graduate students from Georgia Tech and Emory University have decided to respond to the request by submitting a R-21 grant (Exploratory/Developmental Grant, http://grants1.nih.gov/grants/funding/r21.htm).
After a preliminary consideration, the teams have decided to propose an INNOVATIVE, nano-sized “Vulnerable Plaque” FINDER that can detect "vulnerable atherosclerosis plaques" before they rupture in vivo through a real-time imaging method in human. This application is due by Oct. 28th and should include at least following:
Specific Aims
Background
Prototype design and description
Future considerations
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:
- Concentration of therapeutic action exclusively or predominantly at a desired target site;
- Avoidance of biological and biophysical barriers to the penetration and efficacy of the therapeutic action;
- Release of therapeutic action in desired, pre-programmed time-dependent patterns;
- 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;
- 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:
- Molecular assemblies or particulates for diagnostic imaging (smart contrast agents) and targeted therapeutics;
- Molecular assemblies capable of targeted release;
- Implantable systems for controlled actions, including drug release chips and stents;
- Substrates and templates for organ and/or tissue repair;
- Circulating or implantable hybrids comprising biological cells and synthetic elements for tracking, imaging and therapeutics;
- In-vivo assessments, including mechano-chemical sensing technology;
- 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 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