Issue 14, 2024

Lung-selective nucleic acid vectors generated by in vivo lung-targeting-protein decoration of polyplexes

Abstract

Nucleic acid drugs show immense therapeutic potential, but achieving selective organ targeting (SORT) for pulmonary disease therapy remains a formidable challenge due to the high mortality rate caused by pulmonary embolism via intravenous administration or the mucus barrier in the respiratory tract via nebulized delivery. To meet this important challenge, we propose a new strategy to prepare lung-selective nucleic-acid vectors generated by in vivo decoration of lung-targeting proteins on bioreducible polyplexes. First, we synthesized polyamidoamines, named pabol and polylipo, to encapsulate and protect nucleic acids, forming polyamidoamines/mRNA polyplexes. Second, bovine serum albumin (BSA) was coated on the surface of these polyplexes, called BSA@polyplexes, including BSA@pabol polyplexes and BSA@polylipo polyplexes, to neutralize excess positive charge, thereby enhancing biosafety. Finally, after subcutaneous injection, proteins, especially vitronectin and fibronectins, attached to the polyplexes, resulting in the formation of lung-selective nucleic-acid vectors that achieve efficient lung targeting.

Graphical abstract: Lung-selective nucleic acid vectors generated by in vivo lung-targeting-protein decoration of polyplexes

Supplementary files

Article information

Article type
Paper
Submitted
11 Apr 2024
Accepted
21 May 2024
First published
22 May 2024
This article is Open Access
Creative Commons BY-NC license

Biomater. Sci., 2024,12, 3600-3609

Lung-selective nucleic acid vectors generated by in vivo lung-targeting-protein decoration of polyplexes

X. Pu, Z. Li, R. Chen, J. Shi, J. Qin, Y. Zhu and J. Du, Biomater. Sci., 2024, 12, 3600 DOI: 10.1039/D4BM00502C

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