# Macrophage-targeted lncRNA-regulating nanoparticles for glioblastoma treatment

> **NIH NIH R01** · EMORY UNIVERSITY · 2023 · $391,250

## Abstract

There is a critical need to identify mechanisms whereby abnormally regulated lncRNAs in macrophages drive
progression of GBM and ways to target these lncRNAs preclinically. Our long-term goal is to accelerate the
development of immune therapeutics targeting dysregulated lncRNAs to improve outcomes of GBM patients.
Our overall objective for this application is to establish a delivery platform targeting novel GBM-specific
lncRNAs that promote tumor progression. Our central hypothesis is that overexpression of lncRNAs in TAMs
promote GBM tumor progression and immune suppression and are targetable with nanoparticles. The rationale
for the proposed research is that evidence of nanoparticle-based targeting of dysregulated GBM-specific
lncRNAs will provide new opportunities for the continued development of novel treatment strategies focused on
inhibiting TAM-mediated immune suppression. Aim 1: Identify candidate lncRNAs mediating GBM
progression. Our approach will be to perform deep bulk RNASeq of CD14+ cell subsets sorted from single
cell suspensions of fresh GBM tissue and compare these to the peripheral blood of GBM patients and normal
controls to identify differentially expressed lncRNAs, then use bioinformatic tools to choose lncRNAs that are
likely to contribute to GBM immune suppression. Our working hypothesis is that TAMs overexpress lncRNAs
associated with promotion of immune suppression in GBM beyond those identified from PBMCs alone. Aim 2.
Determine the effect(s) of candidate lncRNA depletion on TAM phenotype and function. Our approach
will be to deplete candidate lncRNAs in monocytes using siRNA. We will functionally characterize the response
to depletion of these lncRNAs and begin mechanistic characterization of novel lncRNAs from Aim 1. Our
working hypothesis is that depleting target lncRNAs will change the phenotype and function of these cells,
making them resistant to M2-like polarization by IL-4 and IL-13, maintaining a more immune-stimulating state.
Aim 3. Develop lncRNA targeted theranostic nanoparticles for lncRNA depletion in TAMs. Our approach
will be to further develop MRI trackable nanoparticles for depletion of our preliminary target lncRNAs and any
lncRNAs identified in Aim 1 in our genetically engineered murine model of GBM. Our working hypothesis is that
our nanoparticles will deplete M2-like TAMs in the murine tumors and improve survival in this model. Our
contribution here is expected to be the identification of novel lncRNAs with functional relevance in GBM TAMs
and a translational platform for their delivery in murine models of GBM. These contributions will be significant
because they are expected to represent an important next step toward future development and clinical trials of
novel immune therapeutics for patients with this devastating brain cancer. The proposed research is
innovative, in our opinion, because it represents a substantive departure from the status quo by focusing on
discovery of immune-related lncRNAs...

## Key facts

- **NIH application ID:** 10701432
- **Project number:** 1R01NS132725-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Edjah Nduom
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $391,250
- **Award type:** 1
- **Project period:** 2023-09-21 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701432

## Citation

> US National Institutes of Health, RePORTER application 10701432, Macrophage-targeted lncRNA-regulating nanoparticles for glioblastoma treatment (1R01NS132725-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10701432. Licensed CC0.

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