# Antifungal Imunoliposomes

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2020 · $188,750

## Abstract

Project Summary/Abstract
 Invasive fungal infections cause millions of deaths each year and they are refractory to treatment. Patients
at the greatest risk of developing life-threatening fungal infections have weakened immune systems or various
other lung disorders. Aspergillus fumigatus and related fungal species cause pulmonary invasive aspergillosis.
Even after treatment with antifungals such as amphotericin B (AmB) packaged in liposomes, one-year survival
among immunocompromised patients with invasive aspergillosis is only 25 to 60%. Antifungals are toxic to
patients with numerous side effects and no current treatment clears the lungs of fungi. Without a doubt, there is
room for improving antifungal therapeutics to treat aspergillosis.
 Immunoliposomes are liposomes coated with a monoclonal antibody (mAb) or other protein with specificity
for a surface antigen on target cells, enabling the active delivery of a therapeutic drug to a specific cell type.
Drug loaded immunoliposomes greatly improve cell-type specificity and reduce cytotoxicity such that higher
doses of drug may be delivered to target cells than with liposomes. The overarching goal of this exploratory
proposal is to demonstrate that fungal-cell wall targeted immunoliposomes loaded with antifungal agents have
increased efficacy over drug loaded liposomes. Our experimental hypothesis is that AmB loaded
immunoliposomes coated with monoclonal antibodies or Dectin-1 targeting A. fumigatus cell wall antigens will
show enhanced fungal-specific delivery and antifungal activity over untargeted liposomes.
 Two innovations further our goal. First, we isolated a battery of A. fumigatus cell-wall specific mAbs that
bind differentially to various regions on hyphae, germ tubes and conidia, that will enable targeted delivery of
immunoliposomes to fungi in vitro and in vivo. Second, we furthered the development of simplified protocols for
constructing small batches of fluorescent AmB immunoliposomes and screening methods that will accelerate
our examining various targeted-liposomal formulations to fungi in vitro and in vivo in the lungs of infected mice.
 Our first specific aim is to screen among mAbs and Dectin-1 for targeting protein constructs that achieve
the most efficient uptake of fluorescent AmB immunoliposomes into A. fumigatus cells. Results will be
quantified by fluorescent microscopy, ELISA, and by assaying fungal cell survival. Our second specific aim is
to show that treating infected mice with AmB loaded immunoliposomes targeting A. fumigatus cell wall
component(s) kills more fungal cells and increases mouse survival rates relative to untargeted drug loaded
liposomes. Results will be evaluated by examining the (1) reduction in A. fumigatus viable cell numbers, (2)
alteration in lung pathology, and (3) improvement in mouse survival rates. A team of well acquainted scientists
with expertise in immunology, immunoliposomes, fungal biology and pathology, and biochemistry has been
assemble...

## Key facts

- **NIH application ID:** 9926213
- **Project number:** 5R21AI144498-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Richard Brian Meagher
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,750
- **Award type:** 5
- **Project period:** 2019-05-06 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926213

## Citation

> US National Institutes of Health, RePORTER application 9926213, Antifungal Imunoliposomes (5R21AI144498-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9926213. Licensed CC0.

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