Impacts of PEGylation on the gene and oligonucleotide delivery system

Ikeda, Yutaka; Nagasaki, Yukio

doi:10.1002/app.40293

Cited by 47 publications

(43 citation statements)

References 105 publications

(111 reference statements)

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“…This trend could be explained due to the presence of PEG in the external shell of NP that could stabilize them through inter- and intramolecular interactions 61, 62 . In fact, it is well-known that PEG can also form hydrogen bonds with the aqueous environment and its presence has also multiple advantages such as the effectively protection of NPs against hydrolysis or enzymatic degradation and the prevention of their recognition by RES 63, 64 .…”

Section: Resultsmentioning

confidence: 99%

α-TOS-based RAFT block copolymers and their NPs for the treatment of cancer

et al. 2016

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α-Tocopheryl succinate (α-TOS) is a well-known mitochondrially targeted anticancer compound. However, the major factor limiting the use of α-TOS is its low solubility in physiological media. To overcome this problem, the aim of this work is the preparation of new polymeric and active α-TOS-based nanovehicle with a precise control over its macromolecular architecture. Reversible addition-fragmentation chain transfer polymerization (RAFT) is used to synthesize an α-TOS amphiphilic block copolymer with highly homogeneous molecular weight and relatively narrow dispersity. Macro-chain transfer agents (macro-CTA) based on poly(ethylene glycol) (PEG) of different molecular weights (MW, ranging from 4.6 to 20 kDa) are used to obtain block copolymers with different hydrophilic/hydrophobic ratios with PEG being the hydrophilic block and a methacrylic derivative of α-tocopheryl succinate (MTOS) being the monomer that formed the hydrophobic block. PEG-b-poly(MTOS) form spherical nanoparticles (NPs) by self-organized precipitation (SORP) or solvent exchange in aqueous media enabling to encapsulate and deliver hydrophobic molecules in their core. The resulting NPs are rapidly endocytosed by cancer cells. The biological activity of the synthesized NPs are found to depend on the MW of PEG, with NP comprised of the higher MW copolymer resulting in the lower bioactivity due to PEG shielding inhibiting cellular uptake by endocytosis. Moreover, the biological activity also depends on the MTOS content, as the biological activity increases as a function of MTOS concentration.

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Section: Resultsmentioning

confidence: 99%

α-TOS-based RAFT block copolymers and their NPs for the treatment of cancer

et al. 2016

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“…This was expected, as the IPCs were formed with an excess of PEG by weight, and PEG is known to be cytocompatible. 39, 40 Interestingly, some polycatechol-derived IPCs seem to significantly improve viability or metabolic activity of the non-phagocytic cells. These MTS values were significantly different from those of cells not exposed to microparticles.…”

Section: Resultsmentioning

confidence: 99%

Pseudotannins self-assembled into antioxidant complexes

et al. 2015

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Natural tannins are attractive as building blocks for biomaterials due to their antioxidant properties and ability to form interpolymer complexes (IPCs) with other macromolecules. One of the major challenges to tannin usage in biomedical applications is their instability at physiological conditions and a lack of control over the purity and reactivity. Herein, we report the synthesis and characterization of tannin-like polymers with controlled architecture, reactivity, and size. These pseudotannins were synthesized by substituting linear dextran chains with gallic, resorcylic, and protocatechuic pendant groups to mimic the structure of natural hydrolysable tannins. We demonstrate that these novel materials can self-assemble to form reductive and colloidally stable nanoscale and microscale particles. Specifically, the synthesis, turbidity, particle size, antioxidant power, and cell uptake of IPCs derived from pseudotannins and poly(ethylene glycol) was evaluated.

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“…Our experiments focus on 40 nm gold NPs PEGylated with a methyl-PEG-thiol (5000 Da), a common functionalization scheme for NPs used in biological or biomedical applications. [36][37][38][39][40][41] Based on previous work, [33][34][35] we expected a decrease in corona formation. Our first step was to quantify the amount of serum proteins adsorbed on PEGylated NPs compared to the same NPs lacking PEG.…”

Section: Introductionmentioning

confidence: 94%

PEGylated nanoparticles: protein corona and secondary structure

Runa¹,

Hill²,

Cochran³

et al. 2014

SPIE Proceedings

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Nanoparticles have important biological and biomedical applications ranging from drug and gene delivery to biosensing. In the presence of extracellular proteins, a "corona" of proteins adsorbs on the surface of the nanoparticles, altering their interaction with cells, including immune cells. Nanoparticles are often functionalized with polyethylene glycol (PEG) to reduce this non-specific adsorption of proteins. To understand the change in protein corona that occurs following PEGylation, we first quantified the adsorption of blood serum proteins on bare and PEGylated gold nanoparticles using gel electrophoresis. We find a threefold decrease in the amount of protein adsorbed on PEGylated gold nanoparticles compared to the bare gold nanoparticles, showing that PEG reduces, but does not prevent, corona formation. To determine if the secondary structure of corona proteins was altered upon adsorption onto the bare and PEGylated gold nanoparticles, we use CD spectroscopy to characterize the secondary structure of bovine serum albumin following incubation with the nanoparticles. Our results show no significant change in protein secondary structure following incubation with bare or PEGylated nanoparticles. Further examination of the secondary structure of bovine serum albumin, α2-macroglobulin, and transferrin in the presence of free PEG showed similar results. These findings provide important insights for the use of PEGylated gold nanoparticles under physiological conditions.

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Impacts of PEGylation on the gene and oligonucleotide delivery system

Cited by 47 publications

References 105 publications

α-TOS-based RAFT block copolymers and their NPs for the treatment of cancer

α-TOS-based RAFT block copolymers and their NPs for the treatment of cancer

Pseudotannins self-assembled into antioxidant complexes

PEGylated nanoparticles: protein corona and secondary structure

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