Enhanced Cellular Transduction of Nanoparticles Resistant to Rapidly Forming Plasma Protein Coronas.

Autor: Blokpoel Ferreras LA; Regenerative Medicine and Cellular Therapies Division, The University of Nottingham Biodiscovery Institute (BDI), School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK., Scott D; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Vazquez Reina S; School of Veterinary Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Roach P; Department of Chemistry, Loughborough University, Leicestershire, LE11 3TU, UK., Torres TE; Institute of Nanoscience of Aragón, University of Zaragoza, 50009, Zaragoza, Spain., Goya GF; Institute of Nanoscience of Aragón, University of Zaragoza, 50009, Zaragoza, Spain., Shakesheff KM; Regenerative Medicine and Cellular Therapies Division, The University of Nottingham Biodiscovery Institute (BDI), School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK., Dixon JE; Regenerative Medicine and Cellular Therapies Division, The University of Nottingham Biodiscovery Institute (BDI), School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK.
Jazyk: angličtina
Zdroj: Advanced biosystems [Adv Biosyst] 2020 Oct; Vol. 4 (10), pp. e2000162. Date of Electronic Publication: 2020 Sep 13.
DOI: 10.1002/adbi.202000162
Abstrakt: Nanoparticles (NPs) are increasingly being developed as biomedical platforms for drug/nucleic acid delivery and imaging. However, in biological fluids, NPs interact with a wide range of proteins that form a coating known as protein corona. Coronae can critically influence self-interaction and binding of other molecules, which can affect toxicity, promote cell activation, and inhibit general or specific cellular uptake. Glycosaminoglycan (GAG)-binding enhanced transduction (GET) is developed to efficiently deliver a variety of cargoes intracellularly; employing GAG-binding peptides, which promote cell targeting, and cell penetrating peptides (CPPs) which enhance endocytotic cell internalization. Herein, it is demonstrated that GET peptide coatings can mediate sustained intracellular transduction of magnetic NPs (MNPs), even in the presence of serum or plasma. NP colloidal stability, physicochemical properties, toxicity and cellular uptake are investigated. Using label-free snapshot proteomics, time-resolved profiles of human plasma coronas formed on functionalized GET-MNPs demonstrate that coronae quickly form (<1 min), with their composition relatively stable but evolving. Importantly GET-MNPs present a subtly different corona composition to MNPs alone, consistent with GAG-binding activities. Understanding how NPs interact with biological systems and can retain enhanced intracellular transduction will facilitate novel drug delivery approaches for cell-type specific targeting of new nanomaterials.
(© 2020 The Authors. Published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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