Issue 39, 2022

Tailored polyethylene glycol grafting on porous nanoparticles for enhanced targeting and intracellular siRNA delivery

Abstract

Surface functionalization of nanoparticles with polyethylene glycol (PEG) has been widely demonstrated as an anti-opsonization strategy to reduce protein corona formation which is one of the major concerns affecting target receptor recognition. However, excessive surface passivation with PEG can lead to the strong inhibition of cellular uptake and less efficient binding to target receptors, resulting in reduced potential of targeted delivery. To improve specific cell targeting while reducing the nonspecific protein adsorption, a secondary packaging of the nanoparticles with shorter PEG chains, making the targeting ligands densely stretched out for enhanced molecular recognition is demonstrated. Particularly, we report the tailored surface functionalization of the porous nanoparticles that require the stealth shielding onto the open-pore region. This study shows that, in addition to the surface chemistry, the conformation of the PEG layers controls the cellular interaction of nanoparticles. Since the distance between neighboring PEG chains determines the structural conformation of the grafted PEG molecules, tailored PEG combinations can efficiently resist the adsorption of serum proteins onto the pores by transitioning the conformation of the PEG chains, thus significantly enhance the targeting efficiency (>5-fold). The stretched brush PEG conformation with secondary packaging of shorter PEG chains could be a promising anti-opsonization and active targeting strategy for efficient intracellular delivery of nanoparticles.

Graphical abstract: Tailored polyethylene glycol grafting on porous nanoparticles for enhanced targeting and intracellular siRNA delivery

Supplementary files

Article information

Article type
Paper
Submitted
30 Maijs 2022
Accepted
29 Aug. 2022
First published
12 Sept. 2022
This article is Open Access
Creative Commons BY-NC license

Nanoscale, 2022,14, 14482-14490

Tailored polyethylene glycol grafting on porous nanoparticles for enhanced targeting and intracellular siRNA delivery

J. Yoo, K. Kim, S. Kim, H. H. Park, H. Shin and J. Joo, Nanoscale, 2022, 14, 14482 DOI: 10.1039/D2NR02995B

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