Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Multifunctional nanoformulations for diagnostic imaging of atherosclerosis

Award Number: R44HL110417
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2011
PERIOD OF PERFORMANCE END DATE: 04/30/2017

Group Awards By:

View Award Description

Multifunctional nanoformulations for diagnostic imaging of atherosclerosis - DESCRIPTION (provided by applicant): Despite advances in cardiovascular care, atherosclerosis remains the leading cause of mortality in the United States and worldwide. A vast majority of cardiovascular events such as stroke or myocardial infarction result from rupture or erosion of vulnerable atherosclerotic plaques. These plaques are characterized by high and active macrophage content. Current imaging modalities including magnetic resonance (MR) imaging characterize anatomic and structural features of the plaque rather than its content. Macrophage-specific delivery of gadolinium-based contrast agents (GBCAs) that are often used in cardiovascular MR imaging to enhance contrast between tissues will allow early detection of vulnerable plaques and risk stratification of vulnerable patients. This will also minimize the GBCA dose, thus diminishing the adverse effects of GBCAs. Recently, high density lipoproteins (HDLs) were suggested as delivery nanocarriers for GBCAs. However, unmodified HDL are not normally uptaken by macrophages and require addition of targeting molecules. The approach we are taking to target GBCA-HDL to macrophages involves a naturally occurring oxidation of the major protein of HDL, apolipoprotein (apo) A-I, and eliminates the need for targeting moieties. The long-term objective of the proposed project is to develop a novel approach to early detection and evaluation of vulnerable plaques. In Phase I of this project, we generated and characterized GBCA-HDL formulations that contain oxidized apo A-I, confirmed their target-binding activity in vitro, and demonstrated their specific uptake by intraplaque macrophages in a mouse model of atherosclerosis using in vivo MR imaging and histology. We also generated fully functional GBCA-HDL using synthetic oxidized apo A-I peptides in place of native human apo A-I. This simplifies development of the commercial product and allows to avoid potential clinical and regulatory pitfalls. In Phase II, we propose to more broadly screen GBCA-HDL that contain synthetic oxidized apo A-I peptides, identify the leads and develop the easy-to-scale-up synthetic methodology to allow for clinical-scale manufacture of these agents in liquid and lyophilized form, validate imaging efficacy of the leads in mouse and rabbit models of atherosclerosis, and perform pharmacokinetic, biodistribution and single-dose toxicology studies in two species. A follow-up work will include validation of imaging efficacy of the lead candidates in a porcine model of atherosclerosis, further optimization of the lead formulations and the technology of their manufacture, and the more detailed safety and pharmacokinetic studies required for IND submission. Upon completion of these activities, an IND application will be submitted for clinical testing of GBCA-HDL-enhanced MR in the context of atherosclerosis and coronary artery disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	SIGNABLOK, INC.	61 FRANK ST APT 36	WORCESTER	MA	01604	WORCESTER	USA	Cardiovascular Diseases Research	000	3	7/28/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $673,165 )
2015	2015	SIGNABLOK INC	POST OFFICE BOX 4064	SHREWSBURY	MA	01545	WORCESTER	USA	Cardiovascular Diseases Research	000	3	6/8/2015	NON-COMPETING CONTINUATION	$673,165
														Subtotal = $673,165

Issue Date FY: 2014 ( Subtotal = $669,647 )
2014	2014	SIGNABLOK INC	POST OFFICE BOX 4064	SHREWSBURY	MA	01545	WORCESTER	USA	Cardiovascular Diseases Research	000	2	7/18/2014	COMPETING CONTINUATION	$669,647
														Subtotal = $669,647

Grand Total All Awards = $1,342,812

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Multifunctional nanoformulations for diagnostic imaging of atherosclerosis

Award Number: R44HL110417

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2011

PERIOD OF PERFORMANCE END DATE: 04/30/2017

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer