# Intrathecal delivery of radiation sensitizing nanoparticles in pediatric neuro-oncology

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $617,995

## Abstract

PROJECT SUMMARY / ABSTRACT
Although survival rates for children diagnosed with a primary malignant brain tumor have improved, radiation
induced damage to the developing nervous system remains a significant problem. Few treatment options are
available once malignant cells have metastasized to the leptomeninges that surround the brain and spinal cord.
Leptomeningeal metastasis (LM) cannot be surgically resected, and systemic chemotherapy is hindered by the
presence of the blood-brain and blood-spinal cord barriers, leaving high dose craniospinal radiation as the only
effective treatment option. Some investigators have administered therapeutics directly into the intrathecal space
with the hope that locally administered drugs will better reach LM. However, action of intrathecally administered
agents is limited by rapid clearance and inadequate tissue penetration as cerebrospinal fluid (CSF) turns over.
Furthermore, most traditional chemotherapeutics are poorly water soluble and cannot be administered to the
CSF at relevant concentrations. We have recently developed a novel approach for encapsulating the histone
deacetyle inhibitor (HDACI) quisinostat within biodegradable and biocompatible NPs (QNPs). Our preliminary
data demonstrate that intrathecally administered NPs distribute readily across the surfaces of the brain and
spinal cord, are well retained within the subarachnoid space, and localize with lesions to slow the growth of LM
in a murine model of metastatic medulloblastoma. Here, we propose a comprehensive approach for optimizing
the design of radiation sensitizing NPs for intrathecal drug delivery to treat LM. These NPs serve not just as a
stationary depot to prolong drug presence in the central nervous system but as mobile carriers that we predict
will selectively sensitize metastatic lesions to radiation. We will, (1) engineer the surface of NPs to further improve
their localization with LM, (2), determine the relationship between drug delivery and efficacy in models of
medulloblastoma, and, (3), establish species scaling of direct-to-CSF nanoparticle delivery. Treatments will be
evaluated in patient derived and genetically engineered models of medulloblastoma exhibiting LM. Fluorescent
barcoding, matrix assisted laser desorption ionization (MALDI), and positron emission tomography (PET)
imaging approaches will be used to precisely localize NP and drug delivery to LM with quantitative, cellular-level
resolution. By directly pairing multiple measures of delivery, activity, and efficacy, we expect to develop a
comprehensive understanding of barriers to effective drug delivery within the subarachnoid space. Most
importantly, these studies will advance new nanotechnology toward the clinic for better treatment of pediatric
brain tumors.

## Key facts

- **NIH application ID:** 10200874
- **Project number:** 5R01HD099543-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Rachael W Sirianni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $617,995
- **Award type:** 5
- **Project period:** 2019-08-02 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200874

## Citation

> US National Institutes of Health, RePORTER application 10200874, Intrathecal delivery of radiation sensitizing nanoparticles in pediatric neuro-oncology (5R01HD099543-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200874. Licensed CC0.

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