# Novel nanoparticles function as chemo- and adjunctive-therapy against experimental cerebral malaria

> **NIH NIH R21** · LA JOLLA INFECTIOUS DISEASE INSTITUTE · 2021 · $208,500

## Abstract

Neurological dysfunction is an important complication of blood stage Plasmodium falciparum (Pf) infection and
the syndrome is called cerebral malaria (CM). We have developed human serum albumin (HSA) nanoparticles
(NPs) that are nanoscale aggregates of albumin as a carrier for drug delivery and conjugated anti-bloodstage
Plasmodium drugs, including artemether (A) and artemisinin to these NPs. Our preliminary data indicate that
our novel artemether-conjugated NPs (A-NPs) provide complete protection against experimental CM (eCM).
A-NPs exhibit anti-parasite activity and are preferentially targeted to infected red blood cells (iRBCs) over
uRBCs. Our control NPs (C-NPs), which are NPs without drug, provide significant (p<0.05) protection against
eCM without affecting parasitemia. These findings suggest that A-NPs may exhibit both anti-parasite- and
adjunctive-therapy effects in a single, easy to administer compound.
There is currently no FDA-approved adjunctive therapy of CM to ameliorate the pathogenic host response
during CM and to decrease mortality in the 15-30% of CM patients who die after adequate anti-parasite
chemotherapy. In addition, this adjunctive therapy to ameliorate the pathogenic host response may also
decrease the neurological impairment after Pf infection that results in life-long disability for African children who
survive CM. We use the well-defined, reproducible P. berghei ANKA infection of mice as our model for CM
(i.e., eCM). We hypothesize that our novel nanoparticles protect from development of eCM by
decreasing pathogenic processes leading to eCM, i.e., vasogenic edema, oxidant stress, inflammation,
sequestration, and coagulopathy. The efficacy of NPs as adjunctive therapy against eCM is tested in Aim 1.
Mechanism(s) of action of NPs as adjunctive therapy are tested in Aim 2.
Cerebral malaria is a syndrome comprised of multiple pathogenic processes that includes brain edema, Pf-
infected red blood cell sequestration, oxidant stress, coagulopathy, and inflammation. Vasogenic edema is
observed by magnetic resonance imaging in African children with CM; the vasogenic edema occurs in Indian
adults with CM but is less pronounced. Our preliminary data indicate that C-NPs significantly (p<0.05)
decrease vascular leak measured by Evans Blue dye extrusion into brain during eCM compared with vehicle
controls. A-NPs decreased vascular leak even further than C-NPs to levels similar to those in uninfected mice.
Our preliminary data therefore suggest that NPs function as adjunctive therapy in eCM by reducing vascular
leak. We will also assess the extent to which other key pathogenic mechanisms in eCM are affected by our
eCM-protective NPs. Patients with CM and mice with eCM both exhibit oxidant stress, parasite sequestration,
coagulopathy, and inflammation as possible pathogenic processes, so defining which mechanisms are
significantly decreased by our eCM-protective A-NPs highlights targetable processes for additional future drug
developm...

## Key facts

- **NIH application ID:** 10128323
- **Project number:** 1R21AI151767-01A1
- **Recipient organization:** LA JOLLA INFECTIOUS DISEASE INSTITUTE
- **Principal Investigator:** HENRI C VAN DER HEYDE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $208,500
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128323

## Citation

> US National Institutes of Health, RePORTER application 10128323, Novel nanoparticles function as chemo- and adjunctive-therapy against experimental cerebral malaria (1R21AI151767-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10128323. Licensed CC0.

---

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