# Cancer Stem Cell-Targeted, Silicate Prodrug Nanoparticles to Combat Recurrence

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $298,125

## Abstract

-Drug resistance and tumor recurrence continue to be important challenges affecting the therapeutic
outcomes for breast cancer patients. Recent studies suggest that cancer stem cells (CSCs), a sub-population
of the tumor with `stem cell-like' self-renewal properties, contribute to disease recurrence. Current therapies do
not effectively eradicate CSCs. Our studies show that targeting cytotoxic drugs specifically to CSCs reduces
tumor recurrence in a mouse model of breast cancer. We now propose to build on this exciting finding by
delivering the cytotoxic agent in a nanoparticle formulation that is directed to CSCs using a high affinity
targeting ligand recently developed in one of our laboratories.
 Nanoparticulate delivery systems that are in the size range of ca. 100 nm show enticing tumor
accumulation and intra-tumoral penetration properties. A major limitation of current nanomedicines in this small
size regime, however, is their inability to be formulated to have high drug load levels or sustained drug release,
let alone both. With the support of an R21 award, our team has discovered a novel strategy that uses a
hydrolytically labile silicate ester of paclitaxel (PTX), namely [PTX-Si(OR)3], as a prodrug construct. The
greater hydrophobicity of these silicates, when used in conjunction with flash nanoprecipitation (FNP) as the
means for nanoparticle (NP) synthesis, uniquely allows the preparation of stable, small, block copolymer-
protected NPs containing up to an unprecedented 60-75 wt% of cargo, here the prodrug.
 In an independent thrust, we have successfully developed a single chain variable fragment (scFv) that
recognizes CD133, a unique marker presented on the surface of CSCs. We now propose to marry these two
exciting inventions by developing CD133-targeted (using our new scFv), 100 nm NPs that contain high
percentages of (pro)drug cargo and that show a prolonged duration of payload release. We expect these
formulations to have greatly improved therapeutic efficacy.
 Our Specific Aims are to:
 Aim 1) Develop CSC-targeted, silicate prodrug-loaded NPs that have high drug loading and adjustable
 drug regeneration profiles
 Aim 2) Determine the in vivo safety and efficacy of CSC-targeted, silicate prodrug-loaded NPs.
 Innovations will be enabled by partnering our novel silicate prodrug strategy with FNP technology that,
together, will give small NPs that have high drug loading (>50 wt%) and prolonged timelines for regeneration of
free PTX (a goal is ≥1 week for release of half of the NP payload). Use of the novel CSC targeting ligand
substantially enhances the approach. In addition to developing CSC-targeted NPs as highly effective
anticancer therapeutics, we will advance a fuller understanding of the fundamental relationship between the
physicochemical properties of NPs and their therapeutic performance.

## Key facts

- **NIH application ID:** 10076078
- **Project number:** 7R01EB019893-04
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** THOMAS R. HOYE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $298,125
- **Award type:** 7
- **Project period:** 2017-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076078

## Citation

> US National Institutes of Health, RePORTER application 10076078, Cancer Stem Cell-Targeted, Silicate Prodrug Nanoparticles to Combat Recurrence (7R01EB019893-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10076078. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*