# Targeted Drug Delivery for Spinal Cord Injury Using Retrograde Transport of a Nanoconjugate

> **NIH NIH R61** · WAYNE STATE UNIVERSITY · 2020 · $427,679

## Abstract

This IGNITE Project “Targeted Drug Delivery for Spinal Cord Injury Using Retrograde Transport
of a Nanoconjugate” will develop nanotherapeutics for targeted delivery of drugs to the rostral
ventral respiratory group (rVRG) neurons and phrenic motoneurons for the treatment of
respiratory problems after spinal cord injury. The project team consists of chemical engineers,
spinal cord injury researchers, a biostatistician, and an expert in pharmacology and venture
development. The team has demonstrated complementary and integrated expertise to carry our
all aspects of the project. Respiratory problems including pneumonia, septicemia, and pulmonary
emboli are the leading causes of death in humans after spinal cord injury. Adenosine receptor
antagonist drugs such as 8-cyclopentyl-1,3-diprophyxanthine (DPCPX) can induce respiratory
recovery of the paralyzed hemidiaphragm by activating a latent respiratory motor pathway - the
crossed phrenic pathway. However, the severe side effects of these drugs have prevented their
clinical use. We have demonstrated in our previous work that it may be possible to reduce or even
eliminate the side effects by delivering the drugs selectively to the respiratory neurons using
nanotechnology. Nanotherapeutics promise to improve in vivo drug stability, pharmacokinetics
and biodistribution, and efficacy, all of which can potentially reduce toxicity and side effects. Our
nanotherapeutic design consists of a targeting/transporting protein, wheat germ agglutinin
conjugated to horseradish peroxidase (WGA-HRP), chemically conjugated to a gold nanoparticle
(AuNP), which in turn is chemically conjugated, through a biodegradable bond, to the drug
DPCPX. WGA-HRP is taken up by the terminals of phrenic axons when injected into the
diaphragm muscle of C2 spinal cord hemisectioned rats, and it is retrogradely transported to the
phrenic motoneurons. Importantly, it is further transported transsynaptically across physiologically
active synapses to neurons in the rVRG, and does not transport to any other neuron centers. By
coupling the selective transporter and the drug that induces recovery with a nano-carrier, we can
control the release of the drug in the two caudal neuronal populations that control diaphragm
function. Our targeted drug administration can induce recovery of the paralyzed hemidiaphragm
in rats by using a fraction of the systemic dosage. The IGNITE grant will support early translational
efforts to demonstrate that the nanoconjugate will have sufficient biological activity (i.e., 70%
respiratory function recovery at 4 weeks) while administered at a small fraction of the native drug
dosage (i.e., 0.1%) to warrant further therapeutic development.

## Key facts

- **NIH application ID:** 9990872
- **Project number:** 5R61NS112443-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Guangzhao Mao
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,679
- **Award type:** 5
- **Project period:** 2019-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990872

## Citation

> US National Institutes of Health, RePORTER application 9990872, Targeted Drug Delivery for Spinal Cord Injury Using Retrograde Transport of a Nanoconjugate (5R61NS112443-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990872. Licensed CC0.

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