# LIPOSOME ACTIVATED MACROPHAGES FOR THERAPY OF METASTASIS

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1987 · $77,741

## Abstract

Previous research has indicated that the successful approach to the
treatment of metastasic disease will most likely be a treatment modality
which circumvents the properties of tumor cell heterogeneity and phenotypic
diversity.  There is now an overwhelming body of data demonstrating that
cells of the reticuloendothelial system (RES), e.g. macrophages,
appropriately activated to the tumoricidal state can fulfill the demanding
criteria necessary to obviate these problems.

This project, therefore, is aimed at designing liposomes containing a known
macrophage activator, muramyl dipeptide (MDP), which would selectively
release and deliver the encapsulated compound to cells of the
macrophage-monocyte lineage using mice as the model system.  Previous work
has indicated that monocytes and macrophages specifically phagocytose cells
and liposomes that express phosphatidylserine (PS) in the outer leaflet of
their membranes.  However, the major problem in using negatively charged
liposomes containing PS is that entrapped compounds readily leak from these
particles both in vitro and in vivo.  As a result, only a fraction of the
encapsulated material reaches its primary destination, the macrophage.

This proposal is therefore directed towards the development of a
bifunctional liposome carrier system, using a pH sensitive PS analog which
will 1) specifically home to cells of the RES, and 2) selectively release
their entrapped contents following phagocytosis and acidification inside
the macrophage lysosomal compartments.  Once optimized, this drug-delivery
system will be assessed for its ability to induce macrophage tumoricidal
activity in in vitro system.  Following identification of the optimal
carrier system from these studies, in vivo studies will be performed
encompassing in vivo macrophage activation with in vitro tumoricidal
activity tests, and finally will be assayed for their efficacy in the
treatment of metastatic disease using established mouse model systems.

## Key facts

- **NIH application ID:** 3179706
- **Project number:** 5R01CA040149-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** ALAN Jay SCHROIT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $77,741
- **Award type:** 5
- **Project period:** 1985-09-01 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179706

## Citation

> US National Institutes of Health, RePORTER application 3179706, LIPOSOME ACTIVATED MACROPHAGES FOR THERAPY OF METASTASIS (5R01CA040149-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179706. Licensed CC0.

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