Intravenous Delivery of Lung‐Targeted Nanofibers for Pulmonary Hypertension in Mice

Autor: Kathleen Marulanda, Tristan D. Clemons, Nick D. Tsihlis, Alexandra Mercel, Melina R. Kibbe, Kui Sun, S Ruben Centeno, Erica B. Peters, Mark R. Karver, Sean E. McLean, Samuel I. Stupp, David C. Gillis, Jenna M Weiss, Maria Gambarian, Joshua Roark
Rok vydání: 2021
Předmět:
Zdroj: Adv Healthc Mater
ISSN: 2192-2659
2192-2640
DOI: 10.1002/adhm.202100302
Popis: Pulmonary hypertension is a highly morbid disease with no cure. Available treatments are limited by systemic adverse effects due to non-specific biodistribution. Self-assembled peptide amphiphile (PA) nanofibers are biocompatible nanomaterials that can be modified to recognize specific biological markers to provide targeted drug delivery and reduce off-target toxicity. Here, we developed PA nanofibers that target the angiotensin I-converting enzyme and the receptor for advanced glycation end-products (RAGE), as both proteins are overexpressed in the lung with pulmonary hypertension. We demonstrated that intravenous delivery of RAGE-targeted nanofibers containing the targeting epitope LVFFAED (LVFF) significantly accumulated within the lung in a chronic hypoxia-induced pulmonary hypertension mouse model. Using three-dimensional light sheet fluorescence microscopy, we showed that LVFF nanofiber localization was specific to the diseased pulmonary tissue with immunofluorescence analysis demonstrating colocalization of the targeted nanofiber to RAGE in the hypoxic lung. Furthermore, biodistribution studies showed that significantly more LVFF nanofibers localized to the lung compared to major off-target organs. Targeted nanofibers were retained within the pulmonary tissue for 24 hours after injection. Collectively, these data demonstrate the potential of a RAGE-targeted nanomaterial as a drug delivery platform to treat pulmonary hypertension.
Databáze: OpenAIRE
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