# Renal tubule-specific nanotherapeutics for acute kidney injury

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $269,400

## Abstract

SUMMARY
We propose to develop a method to address the problem of the poor pharmacokinetics and resulting low
efficacy of experimental therapies for acute kidney injury (AKI). AKI accounts for approximately 2% of hospital
admissions in the United States and is associated with increased morbidity and mortality. The prevalence of
AKI is up to 67% in patients admitted to intensive care, with 56% of those progressing to more advanced forms
of the disease. Despite advances in the understanding of the epidemiology and pathogenesis of AKI,
preventive measures remain inadequate and therapeutic approaches have largely proven futile. Multiple drug
trials have been unsuccessful, mainly due to low drug specificity or poor pharmacokinetic profiles. Recently, we
synthesized a novel nanoscale drug delivery platform that selectively targets the nephron (Williams, Nano
Letters, 2015). We found that ‘mesoscale’ nanoparticles target the renal tubules and peritubular endothelium
while bypassing other tissues in the body. The nanoparticles localize up to 25-fold more efficiently in the
kidneys than in any other organ and release their drug cargo while exhibiting no toxic effects on the kidneys or
other organs. This finding is unprecedented, and additional investigations are needed to assess its implications
for the treatment of kidney diseases. We propose to investigate this technology to determine its route to the
tubules, as well as its potential for treating AKI. In service of these these goals, we recently made two
preliminary findings: We characterized in detail a route of entry for exogenous nanomaterials into the renal
tubules and interstitium (Stamatiades, Cell, 2016) mediated by transport through the peritubular capillaries and
monitored by resident macrophages. We hypothesize that our mesoscale nanoparticles internalize by this
peritubular transport route. We propose to address this hypothesis herein. We successfully treated a murine
model of AKI by targeting an ROS inhibitor specifically to the renal tubules. We administered mesoscale
nanoparticles loaded with a radical scavenger, resulting in striking efficacy against a cisplatin-mediated model
of AKI using a dose 154 times lower than that previously shown to treat AKI in a rodent model. We propose to
investigate the mechanism of action of mesoscale nanoparticle-encapsulated ROS inhibitors and to assess
their pharmacologic parameters and efficacy with respect to the inhibitors alone. In Aim 1 of the proposal, we
will characterize the route of nanoparticle uptake in the renal interstitium and tubules. In Aim 2, we will assess
the pharmacologic parameters of kidney-targeted ROS inhibitors. In Aim 3, we will assess the efficacy and
therapeutic mechanism of tubule-specific ROS inhibitor therapy. Outcomes: These studies will address the
unmet need for new methods to improve drug PK in the kidneys for the treatment of AKI by investigating
mesoscale nanoparticle technology. We will determine the route of localiza...

## Key facts

- **NIH application ID:** 9982323
- **Project number:** 5R01DK114321-03
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Daniel Alan Heller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $269,400
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982323

## Citation

> US National Institutes of Health, RePORTER application 9982323, Renal tubule-specific nanotherapeutics for acute kidney injury (5R01DK114321-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9982323. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*