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Developing Nanoplatforms for Co-Delivery of Drugs and Genes to Protect Lung Endothelium from Injury

Award Number: K99HL188210
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Developing Nanoplatforms for Co-Delivery of Drugs and Genes to Protect Lung Endothelium from Injury - PROJECT SUMMARY/ABSTRACT Neonatal and pediatric lung injury is a life-threatening condition associated with high mortality and long-term morbidity. The developing lung is uniquely vulnerable to endothelial cell (EC) injury, apoptosis, and impaired angiogenesis, which compromise lung growth and repair. Currently, no molecularly targeted therapies exist to protect or restore the pulmonary endothelium in this condition. Endothelial dysfunction plays a central role in the pathogenesis of neonatal lung injury, and strategies that both prevent EC death and promote angiogenesis may offer transformative therapeutic benefits. Nanoparticle-based systems capable of delivering both genes (DNA/RNA) and drugs represent a promising therapeutic avenue. Our preliminary data support the idea of designing multifunctional nanoplatforms to co-deliver therapeutic genes and drugs, enabling synergistic protection and repair of the injured lung endothelium. The overall objective of this proposal is to develop nanoplatforms for co- delivery of drugs and genes to protect pulmonary ECs from neonatal lung injury. Our central hypothesis is that combined delivery of anti-apoptotic genes with pro-angiogenic drugs will synergistically enhance EC survival and promote vascular repair. This project is innovative because it integrates materials science, nanomedicine, and pulmonary biology to address a critical unmet need for new therapies in neonatal lung injury. Specific Aims: In Aim1, we will optimize nanoparticle formulations for stability, safety, and endothelial targeting in neonatal lungs. Specifically, we will characterize key physicochemical properties that influence targeting specificity and gene delivery efficiency, evaluate strategies to overcome hydrolytic instability that limits reproducibility, and develop formulations that avoid the concerns associated with “forever chemicals” while maintaining endothelial selectivity. In Aim2, we will assess the ability of optimized NPs to encapsulate hydrophobic small-molecule drugs relevant to lung injury treatment. Next, we will develop and test co- delivery nanoplatforms that encapsulate both genes and drugs while retaining endothelial specificity. Clusterin (CLU), an anti-apoptotic gene decreased during lung injury, will be co- delivered with Leflunomide, a candidate drug that promotes angiogenesis. These platforms will be evaluated in neonatal lung injury models to investigate their capacity to protect ECs, enhance repair, and improve lung function. In addition, we will identify additional gene-drug combinations to uncover synergistic mechanisms critical for endothelial repair after lung injury. By integrating advances in nanoparticle engineering with mechanistic insights into endothelial biology, the proposed studies will establish a foundation for clinically translatable therapies to improve outcomes of lung injury and other EC- associated pulmonary diseases.


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 = $108,950 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Lung Diseases Research	000	1	8/12/2026	NEW	$108,950
														Subtotal = $108,950

Grand Total All Awards = $108,950

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Developing Nanoplatforms for Co-Delivery of Drugs and Genes to Protect Lung Endothelium from Injury

Award Number: K99HL188210

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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