Nanotheranostics 2021; 5(3):309-320. doi:10.7150/ntno.47734

Research Paper

Pulmonary fate and consequences of transferrin-functionalized gold nanoparticles

Nagarjun Venkata Konduru1✉, Karen Velasco-Alzate1, Sitaramaraju Adduri1, Kyryl Zagorovsky2, Daysi Diaz-Diestra3, Faisalina Fisol3#, Marcelo Sanches3, Harrison Ndetan4, Joseph David Brain3, Ramon Morales Molina3

1. Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, 11937 U.S. Hwy 271, Tyler, TX 75708, USA.
2. Luna Nanotech Inc., 439 University Avenue, 5th Floor, Toronto, ON, Canada M5G 1Y8.
3. Center for Nanotechnology and Nanotoxicology, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
4. Department of Biostatistics, University of Texas Health Science Center at Tyler, 11937 U.S. Hwy 271, Tyler, TX 75708, USA.
#Current Address: School of Pharmaceutical Sciences, 11800 Universiti Sains Malaysia, Pulau Pinang, Malaysia.

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Citation:
Konduru NV, Velasco-Alzate K, Adduri S, Zagorovsky K, Diaz-Diestra D, Fisol F, Sanches M, Ndetan H, Brain JD, Molina RM. Pulmonary fate and consequences of transferrin-functionalized gold nanoparticles. Nanotheranostics 2021; 5(3):309-320. doi:10.7150/ntno.47734. Available from https://www.ntno.org/v05p0309.htm

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Abstract

Surface functionalization of nanoparticles (NPs) may alter their biological interactions such as uptake by alveolar macrophages (AMs). Pulmonary delivery of gold NPs (Au NPs) has theranostic potential due to their optoelectronic properties, minimal alveoli to blood translocation, and possibility of specific cell targeting. Here, we examined whether coating Au NPs with transferrin alters their protein corona, uptake by macrophages, and pulmonary translocation.

Methods: Rats were intratracheally instilled with transferrin-coated Au NPs (Tf-Au NPs) or polyethylene glycol-coated Au NPs (PEG-Au NPs). AMs were collected and processed for quantitation of Au cell uptake using ICP-MS and electron microscopy. Au retention in the lungs and other organs was also determined. The uptake of fluorescently labeled Tf-Au NPs and PEG-Au NPs by monocyte-derived human macrophages was also evaluated in vitro.

Results: We showed that Tf-Au NPs were endocytosed by AMs and were retained in the lungs to a greater extent than PEG-Au NPs. Both Au NPs acquired similar protein coronas after incubation in rat broncho-alveolar lavage fluid (BALf). The translocation of Au from both NPs to other organs was less than 0.5% of the instilled dose. Transferrin coating enhanced the uptake of Au NPs by primary monocyte-derived human macrophages.

Conclusions: We report that coating of NP surface with transferrin can target them to rat AMs and human monocyte-derived macrophages. NP functionalization with transferrin may enhance NP-based therapeutic strategies for lung diseases.

Keywords: protein corona, alveolar macrophage, lung clearance, organ retention, primary human monocyte-derived macrophages