Distinct effects of endosomal escape and inhibition of endosomal trafficking on gene delivery via electrotransfection

Cervia, Lisa D.; Chang, Che-Ming; Wang, Liangli; Yuan, Fan

doi:10.1371/journal.pone.0171699

Cited by 50 publications

(53 citation statements)

References 90 publications

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“…We assume that R8 may enhance the interaction between YSK and endosomal membranes, thus leading to a more efficient disruption of endosomes and the release of pDNA to the cytosol. To further confirm this result, we measured transfection activities in the absence and presence of the endosomedisrupting agent, chloroquine (Figure 8) [33]. The disruption of endosomes by chloroquine enhanced the transfection activities in the case of YSK NPs by ~2-fold, indicating that a significant amount of pDNA was trapped in the endosome/lysosome compartment.…”

Section: Endosomal Escape Of Different Nanoparticlesmentioning

confidence: 69%

Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in efficient gene delivery based on double-coated nanoparticles

Khalil

Kimura

Sato

et al. 2018

Journal of Controlled Release

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We report on the development of a highly efficient gene delivery system based on synergism between octaarginine (R8), a representative cell penetrating peptide, and YSK05, a recently developed pH-sensitive cationic lipid. Attaching a high density of R8 on the surface of YSK05 nanoparticles (NPs) that contained encapsulated plasmid DNA resulted in the formation of positively charged NPs with improved transfection efficiency. To avoid the development of a net positive charge, we controlled the density and topology of the R8 peptide through the use of a two-step coating methodology, in which the inner lipid coat was modified with a low density of R8 which was then covered with an outer neutral YSK05 lipid layer. Although used in low amounts, the R8 peptide improved cellular uptake and endosomal escape of the DNA encapsulated in YSK05 NPs, which resulted in a high transfection efficiency. The two-step coating design was essential for achieving a high degree of transfection, as evidenced by the low activity of NPs modified with the same amount of R8 in a regular single-coated design. In addition, a high transfection efficiency was not observed when R8 or YSK05 were used alone, which confirms the existence of a synergistic effect between both components. The results of this study indicate that cationic cell penetrating peptides have the ability to improve transfection activities without imparting a net positive charge when used in the proper amount and in conjunction with the appropriate design. This is expected to significantly increase the potential applications of these peptides as tools for augmenting the activity of lipid nanoparticles used in gene delivery.

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Section: Endosomal Escape Of Different Nanoparticlesmentioning

confidence: 69%

Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in efficient gene delivery based on double-coated nanoparticles

Khalil

Kimura

Sato

et al. 2018

Journal of Controlled Release

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“…Though, there was no change in the buffering capacity when the pH was<2 for both niosomes. Chloroquine might induce endosomal and lysosomal escape via the proton sponge effect [40]. This result could suggest that chloroquinecontaining formulation could increase the proton sponge effect, and therefore, the endosomal escape capacity of DPP80-CQ niosomes.…”

Section: Discussionmentioning

confidence: 95%

Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes

Mashal

Attia

Martı́nez

et al. 2019

Journal of Controlled Release

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“…We also examined the transfection activity of the PEGylated R8-MEND in the presence of the endosome disrupting agent chloroquine in an attempt to identify the effect of PEG on endosomal escape. Chloroquine accumulates in endosomes and eventually causes endosome disruption leading to an enhanced cytosolic release of endocytosed carriers (Cervia et al, 2017). Chloroquine would be expected to fully restore the activity if only endosomal escape is impaired.…”

Section: Mechanism Of Reduced Activity Of Pegylated Mendmentioning

confidence: 99%

An efficient PEGylated gene delivery system with improved targeting: Synergism between octaarginine and a fusogenic peptide

Khalil

Harashima

2018

International Journal of Pharmaceutics

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Because of their ability to translocate different cargos into cells, arginine-rich cell penetrating peptides (CPPs) are promising vehicles for drug and gene delivery. The use of CPP-based carriers, however, is hampered by the lack of specificity and by interactions with negative serum components. Polyethylene glycol (PEG) is used to decrease such non-specific interactions, albeit its use is associated with reduced transfection efficiency. In this study, we describe the development of PEGylated CPP-based gene carrier with an improved targeting and a high transfection activity. The system was prepared by condensing DNA with a polycation followed by coating with a lipid envelope containing the octaarginine (R8) peptide as a model CPP. R8-modified nanoparticles produced high transfection activities, but the efficiency was reduced by PEG shielding. The reduced activity could be fully restored by the addition of a targeting ligand and a pH-sensitive fusogenic peptide. The efficiency of the proposed system is quite high, even in the presence of serum, and shows improved targeting and selectivity. Surprisingly, the effect of the fusogenic peptide was dramatically reduced in the absence of R8. Although shielded, R8 augmented the activity of the fusogenic peptide, suggesting a synergistic effect between the two peptides at the intracellular level.

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Distinct effects of endosomal escape and inhibition of endosomal trafficking on gene delivery via electrotransfection

Cited by 50 publications

References 90 publications

Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in efficient gene delivery based on double-coated nanoparticles

Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in efficient gene delivery based on double-coated nanoparticles

Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes

An efficient PEGylated gene delivery system with improved targeting: Synergism between octaarginine and a fusogenic peptide

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