A display of pH-sensitive fusogenic GALA peptide facilitates endosomal escape from a Bio-nanocapsule via an endocytic uptake pathway

Nishimura, Yuya; Takeda, Koichi; Ezawa, Ryosuke; Ishii, Jun; Ogino, Chiaki; Kondo, Akihiko

doi:10.1186/1477-3155-12-11

Cited by 51 publications

(37 citation statements)

References 20 publications

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“…Moreover, synthetic peptides were constructed to mimic the fusogenic properties of virus-based peptides [125]. Perhaps the most revolutionary synthetic peptide is the GALA, which has pH-sensitive and amphiphilic properties.…”

Section: Biomedical Applications Of Self-assembling Peptide-based mentioning

confidence: 99%

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

et al. 2016

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Self-assembly of peptides can yield an array of well-defined nanostructures that are highly attractive nanomaterials for many biomedical applications such as drug delivery. Some of the advantages of self-assembled peptide nanostructures over other delivery platforms include their chemical diversity, biocompatibility, high loading capacity for both hydrophobic and hydrophilic drugs, and their ability to target molecular recognition sites. Furthermore, these self-assembled nanostructures could be designed with novel peptide motifs, making them stimuli-responsive and achieving triggered drug delivery at disease sites. The goal of this work is to present a comprehensive review of the most recent studies on self-assembled peptides with a focus on their “smart” activity for formation of targeted and responsive drug-delivery carriers.

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Section: Biomedical Applications Of Self-assembling Peptide-based mentioning

confidence: 99%

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

et al. 2016

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“…57 This pH-dependent membrane insertion has been used in living cells to facilitate endosomal escape of both nanocapsule and gene payloads. 54-56 Thus, by appending a membrane-inserting EALA peptide to cryptophane we endeavored to generate a xenon biosensor capable of being “activated” in acidic cell environments to label cell membranes and give large 129 Xe NMR chemical shift changes.…”

Section: Introductionmentioning

confidence: 99%

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

2015

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Here we present a “smart” xenon-129 NMR biosensor that undergoes a peptide conformational change and labels cancer cells at acidic pH. To a cryptophane host molecule with high Xe affinity, we conjugated a 30mer EALA-repeat peptide that is alpha-helical at pH 5.5 and disordered at pH 7.5. The 129Xe NMR chemical shift at rt was strongly pH-dependent (Δδ = 3.4 ppm): δ = 64.2 ppm at pH 7.5 vs. δ = 67.6 ppm at pH 5.5 where Trp(peptide)-cryptophane interactions were evidenced by Trp fluorescence quenching. Using Hyper-CEST NMR, we probed peptido-cryptophane detection limits at low-picomolar (10−11 M) concentration, which compares favourably to other NMR pH sensors at 10−2−10−3 M. Finally, in biosensor-HeLa cell solutions, peptide-cell membrane insertion at pH 5.5 generated a 13.4 ppm downfield cryptophane-129Xe NMR chemical shift relative to pH 7.5 studies. This highlights new uses for 129Xe as an ultrasensitive probe of peptide structure and function, along with potential applications for pH-dependent cell labeling in cancer diagnosis and treatment.

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“…30 Such approaches require that the surface of NPs be conjugated to targeting ligands to increase the odds of particle accumulation at the desired location. 26 In addition, this targeting strategy typically leverages the overexpression of enzymes, decrease in pH, 26,31,32 leakiness of the tissue, and/or enhanced tissue retention of the nanosized particles. 23,29 These features can be exploited to activate the circulating NP drug carriers at the target organ or disease site.…”

Section: Introductionmentioning

confidence: 99%

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Cheng¹,

Kumar²,

Sridhar³

et al. 2016

IJN

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Cardiovascular diseases are facilitated by endothelial cell (EC) dysfunction and coincide with EC glycocalyx coat shedding. These diseases may be prevented by delivering medications to affected vascular regions using circulating nanoparticle (NP) drug carriers. The objective of the present study was to observe how the delivery of 10 nm polyethylene glycol-coated gold NPs (PEG-AuNP) to ECs is impacted by glycocalyx structure on the EC surface. Rat fat pad endothelial cells were chosen for their robust glycocalyx, verified by fluorescent immunolabeling of adsorbed albumin and integrated heparan sulfate (HS) chains. Confocal fluorescent imaging revealed a ~3 µm thick glycocalyx layer, covering 75% of the ECs and containing abundant HS. This healthy glycocalyx hindered the uptake of PEG-AuNP as expected because glycocalyx pores are typically 7 nm wide. Additional glycocalyx models tested included: a collapsed glycocalyx obtained by culturing cells in reduced protein media, a degraded glycocalyx obtained by applying heparinase III enzyme to specifically cleave HS, and a recovered glycocalyx obtained by supplementing exogenous HS into the media after enzyme degradation. The collapsed glycocalyx waŝ2 µm thick with unchanged EC coverage and sustained HS content. The degraded glycocalyx showed similar changes in EC thickness and coverage but its HS thickness was reduced to 0.7 µm and spanned only 10% of the original EC surface. Both dysfunctional models retained six- to sevenfold more PEG-AuNP compared to the healthy glycocalyx. The collapsed glycocalyx permitted NPs to cross the glycocalyx into intracellular spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2 µm and 44% coverage of the ECs, but it was able to reverse the NP uptake back to baseline levels. In summary, this study showed that the glycocalyx structure is critical for NP uptake by ECs and may serve as a passive pathway for delivering NPs to dysfunctional ECs.

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A display of pH-sensitive fusogenic GALA peptide facilitates endosomal escape from a Bio-nanocapsule via an endocytic uptake pathway

Cited by 51 publications

References 20 publications

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

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A display of pH-sensitive fusogenic GALA peptide facilitates endosomal escape from a Bio-nanocapsule via an endocytic uptake pathway

Cited by 51 publications

References 20 publications

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

A “Smart” 129Xe NMR Biosensor for pH-Dependent Cell Labeling

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

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Product

Resources

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A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling