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A Multifunctional Nanoparticle Platform for Galectin-3 Targeted Pulmonary Fibrosis Therapy

Award Number: R01HL182828
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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A Multifunctional Nanoparticle Platform for Galectin-3 Targeted Pulmonary Fibrosis Therapy - ABSTRACT Pulmonary fibrosis (PF) is a debilitating and fatal lung disorder characterized by scarring, affecting >100,000 individuals in the United States. It has no cure. The two drugs approved for PF therapy, pirfenidone (PFD) and nintedanib (NIN), both lack selectivity and require oral administration at high doses, leading to off-target toxicities. We have previously shown that encapsulating drugs within nebulizable nanoparticles (NPs) improves their delivery to and retention in the lungs. NPs can also deliver drug combinations to synergistically target multiple disease pathways for combination therapy. The goal of this proposal is to develop a targeted nanoparticle (NP) – based strategy for the selective inhibition of key profibrotic markers implicated in PF progression, to manage this debilitating condition. We hypothesize that (i) NP-mediated targeted inhibition of Galectin-3 (Gal-3) - a central player in the fibrosis process, will have a potent anti-fibrotic effect compared to unencapsulated therapies, (ii) targeted Gal-3 inhibition and concurrent anti-fibrotic drug release will synergistically inhibit profibrotic biomarker expressions to attenuate fibrosis, (iii) co-delivery of NPs with an extracellular matrix (ECM) modulator will improve tissue penetration and lung residence time of the NPs for sustained therapy. Preliminary investigations by our collaborative research team confirmed NP accumulation in the deep lung tissue and downregulation of pro- fibrotic collagen-1a and Gal-3 markers upon delivery to bleomycin-challenged PF mouse models. Aim 1: Optimization of anti-fibrotic drug-containing Gal-3 targeted PLGA NPs for pulmonary delivery. Building on our prior results, the Gal-3-targeted NPs will be optimized for encapsulation and release of PFD or NIN, enabling combination therapy involving an immediate Gal-3 inhibitory effect and a sustained anti-fibrotic effect. Activated fibroblasts (myofibroblasts) and macrophages, which are key players in PF pathogenesis, will be used to evaluate cytocompatibility, uptake kinetics, and Gal-3 binding and inhibition, and combinatorial effects of the NPs in vitro. Aim 2: Evaluation of synergistic effects of NP-mediated Gal-3 targeting and anti-fibrotic drug release with in vivo models and organ-chip platforms. To enhance rigor, the combinatorial effects of the NPs will be assessed in vivo in two PF mouse models - a bleomycin-challenged model and a TGFβ1 transgenic model. Histology, biomarker analysis, collagen assays and lung function tests will be done to evaluate NP efficacy in both models. NP assessment will also be done in a physiologically relevant PF-on-a-chip system using primary cells. Aim 3: Assessment of NP penetration and retention in fibrotic lung tissue via co-delivery with ECM-remodeling agents. We will incorporate ECM-remodeling agents to enhance drug penetration and anti-fibrotic efficacy in the stiff lung environment. NP diffusion will be assessed in vitro using highly biomimetic fibrotic ECM environments and fibroblast spheroids (to mimic fibroblast foci regions). The results will be validated in vivo in the two pulmonary fibrosis mouse models. This research will establish feasibility of our approach using a multi-pronged NP platform for combinatorial drug delivery, which is a significant advance over current PF therapies.


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 = $405,966 )
2026	2026	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Lung Diseases Research	000	1	8/13/2026	NEW	$405,966
														Subtotal = $405,966

Grand Total All Awards = $405,966

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A Multifunctional Nanoparticle Platform for Galectin-3 Targeted Pulmonary Fibrosis Therapy

Award Number: R01HL182828

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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