nn7b02044_si_001.pdf (3.75 MB)
Effect of Alkylation on the Cellular Uptake of Polyethylene Glycol-Coated Gold Nanoparticles
journal contribution
posted on 2017-05-31, 00:00 authored by Lok Wai
Cola Ho, Wing-Yin Yung, Kwun Hei Samuel Sy, Ho Yin Li, Chun Kit K. Choi, Ken Cham-Fai Leung, Thomas W. Y. Lee, Chung Hang Jonathan ChoiAlkyl groups (CnH2n+1) are prevalent
in engineered bionanomaterials used for many
intracellular applications, yet how alkyl groups dictate the interactions
between nanoparticles and mammalian cells remains incomprehensively
investigated. In this work, we report the effect of alkylation on
the cellular uptake of densely polyethylene glycol-coated nanoparticles,
which are characterized by their limited entry into mammalian cells.
Specifically, we prepare densely PEGylated gold nanoparticles that
bear alkyl chains of varying carbon chain lengths (n) and loading densities (termed “alkyl-PEG-AuNPs”),
followed by investigating their uptake by Kera-308 keratinocytes.
Strikingly, provided a modest alkyl mass percentage of 0.2% (2 orders
of magnitude lower than that of conventional lipid-based NPs) in their
PEG shells, dodecyl-PEG-AuNPs (n = 12) and octadecyl-PEG-AuNPs
(n = 18) can enter Kera-308 cells 30-fold more than
methoxy-PEG-AuNPs (no alkyl groups) and hexyl-PEG-AuNPs (n = 6) after 24 h of incubation. Such strong dependence on n is valid for all serum concentrations considered (even
under serum-free conditions), although enhanced serum levels can trigger
the agglomeration of alkyl-PEG-AuNPs (without permanent aggregation
of the AuNP cores) and can attenuate their cellular uptake. Additionally,
alkyl-PEG-AuNPs can rapidly enter Kera-308 cells via the filipodia-mediated pathway, engaging the tips of membrane protrusions
and accumulating within interdigital folds. Most alkyl-PEG-AuNPs adopt
the “endo-lysosomal” route of trafficking, but ∼15%
of them accumulate in the cytosol. Regardless of intracellular location,
alkyl-PEG-AuNPs predominantly appear as individual entities after
24 h of incubation. Our work offers insights into the incorporation
of alkyl groups for designing bionanomaterials for cellular uptake
and cytosolic accumulation with intracellular stability.
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Kera -308 keratinocytesalkyl mass percentageuptakebionanomaterialKera -308 cellsKera -308 cells 30-Polyethylene Glycol-Coated Gold Nanoparticles Alkyl groupspolyethylene glycol-coated nanoparticlesintracellularincubationNPalkyl-PEG-AuNPalkyl groupsserumcarbon chain lengths24 hPEGylated gold nanoparticles
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