# Water Soluble Polymers to Target Tumor-Associated Extracellular Matrix for Delivery of MMP Inhibitors

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $30,036

## Abstract

Project Summary/Abstract. Breast cancer is among the most frequently diagnosed cancers. It accounts for
nearly a quarter of all cancer diagnoses worldwide every year. Metastasis typically occurs early in breast
cancer, and it is the most significant cause of mortality. The current treatment and staging for breast cancer are
based on the TNM prognostic markers: tumor size (T), presence of lymph nodes (N), and metastasis (M).
Increasing evidence indicates that breast cancer development is correlated with significant changes in the
extracellular matrix (ECM). An important change is the excess accumulation and deposition of collagen,
termed desmoplasia, which results in increased linearity of fibrous protein in the tumor-associated ECM, as
well as stiffening of the matrix. These changes are highly correlated with and, based on increasing evidence,
causative of metastasis. A key player that is responsible for this restructuring of the ECM is matrix
metalloproteinases (MMPs), a zinc-dependent family of proteases which break down proteins in the ECM.
There have been efforts to therapeutically combat this propensity for metastasis through the use of MMP
inhibitors as a form of cancer therapy. One highly promising investigational drug is Batimastat, an MMP
inhibitor which progressed through Phases I, II, and III clinical trials, before being eliminated due to poor
solubility and problematic routes of administration. The key limiting factor of Batimastat was in delivery. To
improve this, this study proposes to develop a water-soluble polymer as a vehicle for delivery of Batimastat. N-
(2-hydroxypropyl)methacrylamide (HPMA) copolymers are water soluble, non-toxic, non-immunogenic,
multifunctional polymer platforms, which have been studied extensively for drug delivery. Collagen mimetic
peptide (CMP) is collagen-resembling peptide that was rationally designed to bind to denatured collagen in the
same hallmark triple helical form as endogenous collagen. As collagen is the most abundant protein in
mammals and is the most concentrated molecule in the ECM, the presence of excessive denatured collagen in
the remodeling tumor-associated ECM provides an excellent opportunity for tumor-selective targeting. We
hypothesize that through the incorporation of CMP as a targeting moiety in the side chains of HPMA
copolymers, we can improve the delivery and efficacy of the therapeutic, Batimastat as well as imaging agents.
To test this hypothesis the following Specific Aims will be pursued:  1) to design and characterize a
multifunctional HPMA-CMP conjugate with the ability to bind to tumor-associated ECM; 2) to characterize the
ability of the polymer conjugate systems to modulate tumor cell migration and invasion, [collagen remodeling,
and MMP activity] in vitro; and 3) to evaluate the ability of the polymer conjugate to accumulate in tumor
regions and affect tumor growth [and metastasis].

## Key facts

- **NIH application ID:** 10162529
- **Project number:** 5F31CA213901-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Nithya Subrahmanyam
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,036
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162529

## Citation

> US National Institutes of Health, RePORTER application 10162529, Water Soluble Polymers to Target Tumor-Associated Extracellular Matrix for Delivery of MMP Inhibitors (5F31CA213901-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10162529. Licensed CC0.

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