# Macrophage-specific nanotherapy for breast cancer

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2020 · $514,198

## Abstract

PROJECT SUMMARY/ABSTRACT
Healthy ‘phagocytosis’ — a process by which foreign cells such as tumor cells and apoptotic debris are
engulfed and removed by inflammatory monocytes and macrophages — is a defense against cancer, including
breast cancer. However, phagocytosis against cancer can become inhibited by ‘don’t eat me’ signaling caused
by overexpression of CD47 on the surface of solid tumor cells.
Remarkably, anti-CD47 antibodies can restore phagocytosis of tumor cells, causing tumors to shrink or
stabilize. Unfortunately, these antibodies may also sometimes have severe side effects, especially anemia and
reticulocytosis.
This project addresses the challenge of restoring phagocytosis against solid tumors via the CD47 pathway
without the side effects of anti-CD47 antibodies. We will do this by testing nanoparticles we developed to
selectively deliver small molecule inhibitors of the enzyme SHP1 intracellularly into inflammatory monocytes
and macrophages within breast tumors. SHP1 is part of the CD47 signaling pathway within macrophages and
an excellent target for restoring phagocytosis without side effects.
Strong evidence indicates our nanoparticles can act as a kind of Trojan horse to deliver small molecule drugs
selectively into inflammatory monocytes and macrophages that infiltrate solid tumors. We will reveal the
mechanisms of: A) selective nanoparticle uptake; and B) in vivo nanoparticle delivery of SHP1 inhibitors in 2
murine breast cancer models. Aim 1 will identify the nanoparticle uptake receptor and elucidate the
mechanisms of nanoparticle uptake and persistence in tumors. Aim 2 will test nanoparticles for selectively
releasing SHP1 inhibitors inside inflammatory macrophages, then restoring phagocytosis and shrinking tumors
in vivo without causing anemia and reticulocytosis.
Impact: This project will advance understanding of the CD47 pathway in cancer, develop an intracellular
therapeutic approach to inhibit CD47-related signaling, help remove a major barrier to progress in oncology —
the lack of selective drug delivery into inflammatory monocytes and macrophages, and advance design
principles for translational therapies based on in vivo immune cell selectivity.

## Key facts

- **NIH application ID:** 10052624
- **Project number:** 1R01CA244491-01A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Bryan Ronain Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $514,198
- **Award type:** 1
- **Project period:** 2020-09-04 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052624

## Citation

> US National Institutes of Health, RePORTER application 10052624, Macrophage-specific nanotherapy for breast cancer (1R01CA244491-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10052624. Licensed CC0.

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