# Infection-homing nanosystems as antibacterial therapeutics-delivery platforms

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $788,842

## Abstract

PROJECT SUMMARY
Staphylococcus aureus and Pseudomonas aeruginosa are the leading causes of hospital-acquired infections
and contribute significantly to morbidity and mortality [3, 4]. Standard treatment of infection entails repetitive
high-dose administrations of antibiotics, but the treatment is often rendered ineffective due to poor delivery to
sites of infection and drug resistance mechanisms preventing antibiotic access to intracellular drug targets (e.g.
the drug-impermeable cell wall in gram-negative P. aeruginosa) [5, 6]. Skin infections that have invaded down
to the muscles and fibers are also difficult-to-reach by free-antibiotic formulations and require surgical
treatment [7]. The obstacles we tackle in this proposal are: (1) loss of antibiotics to non-infected tissues; (2)
rapid clearance of small molecule antibiotics by renal and gastrointestinal clearance; (3) poor penetration of
drugs past the bacterial cell wall. We hypothesize that loading antibiotics into longer-circulating nanovehicles
that will home to sites of infection and subsequently facilitate drug uptake into cells/bacteria of interest can
overcome the abovementioned challenges. Here, we propose to develop such nanoplatforms through three
major aims. In Aim 1, we will use in vivo phage display to identify peptides that will home to the bacteria of
interest and/or infected tissue. We will focus specifically on S. aureus and P. aeruginosa infections in models of
deep skin (invasion in muscles and fibers) infection and pneumonia in mice. In the event that direct bacteria-
targeting proves to be difficult, we will also look at peptides that bind selectively to infected tissues and host
cells surrounding the bacterial colonies, as well as macrophage-targeting peptides. As these peptides are to be
conjugated to nanoparticle surfaces, we will then investigate the binding properties of the peptides in singular
and multivalent forms. In Aim 2, we will engineer two nanoplatforms: (1) peptide-based agents that can
selectively penetrate the bacterial membrane (i.e. peptide permeation agents) to which small molecule drugs
will be tethered for increased uptake and (2) porous silicon nanoparticles (pSiNP) to load drugs that have poor
delivery to sites of infection due to unfavorable physicochemical properties (hydrophobic, highly ionic, etc).
These nanoplatforms will be targeted to sites of infection using peptides we have previously discovered or
additional peptides to be identified in Aim 1. Model drugs with poor in vivo antibacterial activity will be loaded
and optimal platforms selected based on drug loading, release kinetics, and cellular uptake for in vivo
pharmacokinetics. In addition to individual pSi- and peptide-based nanoplatforms, we will develop a combined
system in which bacteria-penetrating drug conjugates are loaded into targeted pSi nanoparticles with the goal
of enhanced efficacy. Finally, Aim 3 will focus on the therapeutic performance of lead nanoplatform candidates
...

## Key facts

- **NIH application ID:** 9953945
- **Project number:** 5R01AI132413-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** SANGEETA N. BHATIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $788,842
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953945

## Citation

> US National Institutes of Health, RePORTER application 9953945, Infection-homing nanosystems as antibacterial therapeutics-delivery platforms (5R01AI132413-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953945. Licensed CC0.

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