# Single Cell In Vivo Imaging Technology to Analyze Taxane Nano Formulations in Breast Cancer

> **NIH NIH R00** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $249,000

## Abstract

This proposal aims to develop a novel platform for imaging taxane nano formulation delivery and
pharmacodynamic response at the single-cell level in breast cancer, and apply it to understand the impact of
passive and active molecular targeting of therapeutic nanoparticles (TNPs). TNPs have been developed to
deliver cytotoxic chemotherapies to tumors more safely and effectively; however, clinical trial results often
show equivocal efficacy, largely owing to heterogeneous TNP tumoral accumulation across patients. Thus, a
clear need exists to better understand why many TNP strategies fail in vivo and not result in significantly
improved tumoral uptake or therapeutic response. Advanced in vivo imaging allows unique insight into TNP
behavior at the single-cell level within tumors: in preliminary work, the candidate Dr. Miles Miller has developed
in vivo imaging techniques to uncover a new paradigm for TNP-mediated drug delivery, whereby tumor-
associated macrophage (TAM) serve as drug reservoirs that accumulate nanoparticle vehicle and gradually
release the drug payload to neighboring tumor cells. TAM imaging using companion magnetic nanoparticles
and MRI predicts TNP delivery and efficacy across heterogeneous cohorts, thus showing promise as tool for
patient selection into TNP clinical trials. This proposal hypothesizes that nano-formulation will dramatically
alter how taxanes accumulate at the single-cell level, and that TAM will drive distribution of even so-called
“tumor-targeted” TNPs that have been coated with ligands binding over-expressed proteins on tumor cells. The
proposal addresses questions including i) what are the rate-limiting barriers to TNP delivery and action at the
single-cell level in breast cancer?, ii) to what degree does molecular targeting improve delivery and action of
taxanes?, and iii) can this be combined with other strategies, particularly those related to TAM? In aim 1, a
breast cancer imaging platform will be developed and applied to test passively accumulating TNPs (with no
molecular targeting). In aim 2, multi-channel in vivo imaging will be used to study the impact of TNP
molecular-targeting, for instance using anti-HER2 antibody-labeled TNP in HER2+ breast cancer models. Dr.
Miller has extensive engineering experience in computational analysis of biological variables, new intravital
imaging strategies and in multivariate statistics. With this proposal, he aims to undergo structured training in
cancer biology, molecular biology, immunology, responsible research conduct, and laboratory management as
he transitions to an independent career at the interface of cancer nanotechnology and systems pharmacology.
Work will be conducted in the Center for Systems Biology at Massachusetts General Hospital and Harvard
Medical School under the primary mentorship of Dr. Ralph Weissleder MD, PhD. Dr. Miller has also brought in
co-mentor Prof. Tim Mitchison, expert in taxane pharmacology; Advisory Committee member Dr. Keith
Flaherty, cl...

## Key facts

- **NIH application ID:** 9966899
- **Project number:** 5R00CA207744-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Miles A Miller
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966899

## Citation

> US National Institutes of Health, RePORTER application 9966899, Single Cell In Vivo Imaging Technology to Analyze Taxane Nano Formulations in Breast Cancer (5R00CA207744-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9966899. Licensed CC0.

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