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Nanoparticle Mediated Drug Delivery for Lung Transplantation

P. M. Patel1, S. Jung2, C. L. Miller1, J. M. O1, T. Costa1, A. Dehnadi1, I. Hanekamp1, X. F. Li2, L. Jiang2, H. Ichimura2, A. Azimzadeh1, J. C. Madsen3, R. Abdi2

1Surgery, Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 2Medicine, Transplant Research Center, Brigham and Women's Hospital, Boston, MA, 3Surgery, Center for Transplantation Sciences, Division of Cardiac Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA

Meeting: 2021 American Transplant Congress

Abstract number: 307

Keywords: Immunosuppression, Lung, Perfusion solutions

Topic: Basic Science » Biomarker Discovery and Immune Modulation

Session Information

Session Name: Biomarkers and Cellular Therapies

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 8, 2021

Session Time: 4:30pm-5:30pm

 Presentation Time: 5:00pm-5:05pm

Location: Virtual

*Purpose: Severe primary graft dysfunction (PGD) affects 30% of lung transplant patients. Pulmonary alveolar macrophages play a significant role in lung PGD, but systemic immunotherapy is inadequate in suppressing them. We explored using nanoparticles (NP) as a means of direct allograft immunosuppression delivery.

*Methods: We encapsulated Alexa 594 dye and anti-IL6 receptor monoclonal antibody in poly (lactic-co-glycolic acid) NPs via double emulsion (anti-IL6R-Alexa 594 NP). The lung from one cynomolgus macaque was procured then underwent infusion of lung preservation solution mixed with nanoparticles via direct pulmonary artery cannulation. Samples pre- and post-NP infusion were taken and stained using immunofluorescence techniques. Tissues were stained with antibodies against CD163, vWF, CD11b, CDC11c, HLADR+, CD3, and CD20.

*Results: Hydrodynamic size of anti-IL6R-Alexa594 NP was 107 ± 14 nm (polydispersity index: 0.25), transmission electron microscopy size was 98 ± 8.1 nm, and zeta-potential was -3.1 ± 1.2 mV. We confirmed loading efficiency of anti-IL6R-mAb in NP as 23.1 ± 3.8% using bicinchoninic assay. Anti-IL6R-Alexa594 NP showed 50% of drug elution by 4.6 days and 75% of drug elution by 13 days . Anti-IL6R-Alexa594 NP were found in the lung parenchyma and in the hilar lymph nodes. Immunofluorescence staining assay demonstrated that CD163+, CD11b+, HLADR+, and CD11c+ cells from hilar lymph node internalized NPs. The same held true for the lung parenchyma tissue with the addition of CD3+ cells also having nanoparticle uptake. Approximately 10% of the lymph node macrophages (HLADR+, CD11b+, CD163+) and 50% of the pulmonary macrophages had NP uptake. Figure 1: Immunofluorescence imaging of lung parenchyma. Blue = DAPI, Green = HLADR+, Red = NP.

*Conclusions: In this study, we synthesized bright nanovesicles to track the fate of NPs in the lung. These biocompatible NP produced sustained release of their loaded anti-IL6R over the span of two weeks in physiological condition, offering a way to control immune reactions locally. Despite the short perfusion time, a significant number of lung alveolar macrophages were able to phagocytose NPs. This is a promising new avenue for drug delivery in hopes of reducing incidence and severity of lung PGD.

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To cite this abstract in AMA style:

Patel PM, Jung S, Miller CL, O JM, Costa T, Dehnadi A, Hanekamp I, Li XF, Jiang L, Ichimura H, Azimzadeh A, Madsen JC, Abdi R. Nanoparticle Mediated Drug Delivery for Lung Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/nanoparticle-mediated-drug-delivery-for-lung-transplantation/. Accessed May 9, 2025.

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