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

MMP responsive polymeric materials for treating acute myocardial infarction

Award Number: R01HL139001
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2027

Group Awards By:

View Award Description

MMP responsive polymeric materials for treating acute myocardial infarction - Summary Heart failure (HF) remains the leading cause of death in the U.S., and the rest of the western world. Approximately 37% of myocardial infarction (MI) patients will die from HF within 1 year, and of those who do survive, two-thirds do not make a complete recovery. Each year it is estimated that ~550K Americans will have a new MI, and ~200K will have a recurrent MI, leading to a large body of patients suffering from HF.1 Therefore, our long-term goal is the development of new, minimally invasive, targeted biomaterial based therapies for the treatment of acute MI (AMI), thereby limiting the number of patients that progress to HF. Over the past two decades, there has been significant progress in the development injectable biomaterials that stimulate endogenous repair on their own or through the controlled release of additional therapeutics. This approach is attractive since potential therapies could be delivered minimally invasively via catheter, would be off the shelf and cost-effective, and in the case of therapeutic delivery, would provide targeted delivery limiting systemic off- target effects that plague traditional pharmaceuticals. However, direct injection of these biomaterials, either through minimally invasive surgery or percutaneous transendocardial injection, is unlikely to be translated to AMI patients because of serious safety concerns with the injection procedures, thereby missing the critical therapeutic window immediately post-MI. Together, the PIs developed enzyme-responsive, injectable nanoparticles (NPs), capable of responding to matrix metalloproteinases (MMPs) associated with AMI. The particles accumulate efficiently in infarcted myocardium following systemic administration, by virtue of an enzyme-induced phase transition from small NP to micron-sized scaffold. While we had initial success with this system and observed better targeting compared to traditional modalities, this system suffers the same drawback as most nanoparticles, which have significant off-target accumulation, as they are phagocytosed and transported to the liver following opsonization. Leveraging our success with the general MMP responsive targeting strategy, we propose that a new MMP responsive material comprised of a completely aqueous soluble polymer displaying therapeutic peptides at high densities will have superior biodistribution patterns nanoparticles. Upon systemic administration, these polymers exhibit exceptionally favorable pharmacokinetics (week-long half-lives) and biodistribution characterized by kidney clearance combined with very little liver/spleen accumulation. These polymers are protein like in molecular weight (MW), physicochemical properties and size. They are therapeutic proteomimetic polymers, designed to accumulate at the site of AMI. Here, we aim to develop new MMP responsive polymeric systems (termed protein-like polymers, PLPs) and demonstrate proof-of-concept for using these novel biomaterials for the targeted delivery of therapeutics for AMI.


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: 2026 ( Subtotal = $568,165 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	8	7/6/2026	NON-COMPETING CONTINUATION	$568,165
														Subtotal = $568,165

Issue Date FY: 2025 ( Subtotal = $580,572 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	7	8/15/2025	NON-COMPETING CONTINUATION	$580,572
														Subtotal = $580,572

Issue Date FY: 2024 ( Subtotal = $569,855 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	001	6	7/15/2024	NON-COMPETING CONTINUATION	$569,855
2024	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	4	11/22/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $569,855

Issue Date FY: 2023 ( Subtotal = $597,347 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	5	6/29/2023	COMPETING CONTINUATION	$597,347
														Subtotal = $597,347

Issue Date FY: 2020 ( Subtotal = $387,500 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	4	8/3/2020	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $387,500

Issue Date FY: 2019 ( Subtotal = $387,500 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	3	8/15/2019	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $387,500

Issue Date FY: 2018 ( Subtotal = $387,500 )
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	2	8/9/2018	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $387,500

Issue Date FY: 2017 ( Subtotal = $387,500 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	1	8/1/2017	NEW	$387,500
														Subtotal = $387,500

Grand Total All Awards = $3,865,939

Top

All Categories

About

Search

Reports

Data Submission

Award Information

MMP responsive polymeric materials for treating acute myocardial infarction

Award Number: R01HL139001

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer