Monday, December 29, 2025 12/29/2025

Macrophage-targeting Nanoplatforms as Immunotherapy against Pulmonary Infections

Award Number: R01AI132413
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2028

Group Awards By:

View Award Description

Macrophage-targeting Nanoplatforms as Immunotherapy against Pulmonary Infections - PROJECT SUMMARY New strategies to combat pneumonia caused by different pathogens are urgently needed. Inflammatory macrophages play an essential role in clearing bacteria, fungi, and viruses during infections; however, hyperinflammatory responses mediated by these cells can cause severe side effects, including death. Immunotherapy that modulates macrophage polarization has shown promise in suppressing hyperinflammatory responses while retaining the capability of macrophages to clear pathogens. To achieve successful immunotherapy with RNA therapeutics, the following obstacles must be overcome: (1) rapid clearance of RNA therapeutics by RNase in tissues; (2) poor cellular uptake of free RNA therapeutics; and (3) loss of RNA therapeutics to non-infected tissues and potential off-target side effects. We previously discovered and successfully transitioned to industry two nanotherapeutic systems that addressed these limitations for bacterial infections. The elements of the nanosystems relevant to the present proposal are: high loading capacity for RNA therapeutics; an ability to protect the RNA payload from degradation in vivo; and highly selective targeting of the macrophages via pendant peptides. The proposed project hypothesizes that this approach may be generally applicable across a spectrum of pathogens, and it aims to investigate treatment of viral and fungal pulmonary infections. To address these goals, a deeper understanding of macrophage function and nanoparticle interactions is needed, particularly in the context of pathogenic infections. Through three Specific Aims, we propose to optimize and then evaluate three major nanoplatform-based systems that have shown promise for nucleic acid delivery, and investigate the in vivo biological interactions of the targeted nanoplatforms to obtain deeper understanding of macrophage polarization in combating pulmonary infections: (1) Develop a targeting strategy for macrophage homing in infected lungs. We hypothesize designs that will allow the nanoparticle to reach the infected regions of the lungs while preserving the potency of the RNAi therapeutic, either by i.v. or by direct pulmonary delivery of nanoplatforms. This Aim will focus on screening for new peptides that target macrophages in lung infection models, using the existing macrophage-targeting peptide CRV as a benchmark. We will focus on well-established mouse models of pneumonia induced by carbapenem-resistant K. pneumoniae, A. fumigatus, and influenza A. (2) Develop, evaluate, and then downselect from three broad classes of nanoplatforms (i.e., lipid nanoparticles, tandem peptide nanoparticles, and fusogenic porous silicon nanoparticles) to load RNA therapeutics. These nanoplatforms will be targeted to macrophages in the infected lungs using peptides from Aim 1. Cytotoxicity, gene knockdown efficiency, and macrophage polarization will be evaluated in vitro. Pharmacokinetics including macrophage targeting and tissue distribution will be studied in vivo. (3) Evaluate leading candidate(s) from Aim 2 for therapeutic performance in vivo through intranasal or nebulizing administration. The goal of this Aim is to evaluate biosafety and therapeutic efficacy (i.e., pathogen burden clearance, tissue recovery, and improved survival). The significance of this project is that it will yield tools to actively target macrophages at infected lungs and it will identify the essential design rules for nanoplatforms that can provide immunotherapy to combat a wide range of pulmonary infections.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $642,847 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	8	12/9/2025	NON-COMPETING CONTINUATION	$642,847
														Subtotal = $642,847

Issue Date FY: 2025 ( Subtotal = $649,115 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	7	11/20/2024	NON-COMPETING CONTINUATION	$649,115
														Subtotal = $649,115

Issue Date FY: 2024 ( Subtotal = $684,136 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	6	1/11/2024	COMPETING CONTINUATION	$624,672
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	6	6/10/2024	COMPETING CONTINUATION	$59,464
2024	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	5	6/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $684,136

Issue Date FY: 2021 ( Subtotal = $784,101 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	6/28/2021	NON-COMPETING CONTINUATION	$784,101
														Subtotal = $784,101

Issue Date FY: 2020 ( Subtotal = $788,842 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	6/30/2020	NON-COMPETING CONTINUATION	$788,842
														Subtotal = $788,842

Issue Date FY: 2019 ( Subtotal = $800,521 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	3	6/13/2019	NON-COMPETING CONTINUATION	$800,521
														Subtotal = $800,521

Issue Date FY: 2018 ( Subtotal = $805,479 )
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	6/25/2018	NON-COMPETING CONTINUATION	$805,479
														Subtotal = $805,479

Issue Date FY: 2017 ( Subtotal = $836,708 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	6/26/2017	NEW	$836,708
														Subtotal = $836,708

Grand Total All Awards = $5,991,749

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Macrophage-targeting Nanoplatforms as Immunotherapy against Pulmonary Infections

Award Number: R01AI132413

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer