# Development of nanoparticulate solution for cancer treatment by breakup of tumor extracellular hydroxyapatite: a new paradigm

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $472,960

## Abstract

Hydroxyapatite (HAP), Ca10(PO4)6OH2, once thought to be solely an ubiquitous component of bone, has
not only been shown to be directly produced by breast malignancies. We have expanded the study of tumor
extracellular HAP and present results showing that not only is it present in many other types of malignancies
such as prostate, colon, ovarian, glioma, lung, pancreatic, and gastric cancers but also can be used as an
imaging biomarker for detecting tumor burden. Further, HAP is a potential novel target for therapy. From tumor
detection perspective, we have shown that tumor extracellular HAP can be detected with radioligands that bind
to HAP including 18F-labeled sodium fluoride (18F-NaF) and 99mTc-labeled methyl diphosphate (99mTc-MDP),
imaged by positron emission tomography (PET) and single photon emission computer tomography (SPECT),
respectively. As HAP is absent from normal soft tissue, detection of tumor-associated HAP exhibited both high
specificity and a high signal-to-background ratio.
 With HAP as a potential novel target for treating cancer, we postulated that if HAP-associated calcium
within the tumor microenvironment could be depleted in vivo, then the release of the associated (PO4) - + OH-
anions might induce localized acute extracellular alkalosis in the tumor leading to tumor cell death. Such re-
engineering of the tumor microenvironment by depleting HAP may provide a novel paradigm for cancer
treatment. To test this hypothesis, we developed an injectable nanoparticulate sulfonated polystyrene solution
(NSPS) formulation designed for in vivo delivery. Preliminary work shows that in vivo administration of NSPS in
xenograft mouse models of breast, prostate and colon cancer resulted in the reduction of tumor metabolism
and increased cellular apoptosis without evident systemic adverse effects. Furthermore, in accord with our
hypothesis, the overall acidity (macro pH) of homogenized tumor tissue harvested from NSPS-treated mice
was found to be significantly higher than in tumors from mice that received either vehicle injections or no
injection. In this work, we aim to test the postulate that NSPS leads to tumor extracellular alkalosis by directly
measuring tumor extracellular pH both in vitro, using the ratiometric pH indicator 5-(and-6)-Carboxy SNARF-5
in tumor spheroids, and in vivo with localized 31P spectroscopy of 3-aminopropylphosphonate (3-APP)
quantified by magnetic resonance imaging (MRI) following NSPS treatment. We will correlate changes in
extracellular pH with changes in tumor growth, metabolic activity and cellular apoptosis (Aim 1). In addition, we
will measure the pharmacokinetic (PK) parameters of NSPS in mice and potential markers of toxicity in mouse
models (Aim 2). Planned studies will provide insight into the mechanism for NSPS efficacy versus tumor cells
in a broad range of cancer types, postulated to be mediated via reduction in acidity of the extracellular matrix in
the tumor microenvironment. The goal is to ini...

## Key facts

- **NIH application ID:** 10218793
- **Project number:** 1R21CA252629-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Mohammed Noor Tantawy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $472,960
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218793

## Citation

> US National Institutes of Health, RePORTER application 10218793, Development of nanoparticulate solution for cancer treatment by breakup of tumor extracellular hydroxyapatite: a new paradigm (1R21CA252629-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10218793. Licensed CC0.

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