Influence of the glycocalyx and plasma membrane composition on amphiphilic gold nanoparticle association with erythrocytes

Atukorale, Prabhani U.; Yu, Yingmin; Bekdemir, Ahmet; Carney, Randy P.; Silva, Paulo; Watson, Nicki; Stellacci, Francesco; Irvine, Darrell J.

doi:10.1039/c5nr01355k

Cited by 51 publications

(48 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent results over five experiments suggest that the NP internalization that we observed is global and that the subcellular localization of the AuNP is statistically relevant. While others have reported a similar increase in nanoscale particle permeability for other cell types and conditions, 18,34,47,48 to our knowledge, this is the first time the experiment has been conducted with nonactively targeted AuNP in RFPEC with the intracellular localization identified. Additionally, previously published studies did not attempt to repair the glycocalyx, but only compared the healthy glycocalyx to the degraded glycocalyx.…”

Section: Resultsmentioning

confidence: 91%

“…Previous studies suggest that the outer region of the glycocalyx consists largely of hyaluronan and sialic acid, which are two other important components of the glycocalyx. 10,18,34,44 These glycocalyx elements were not explored in the present study, although their roles and the roles of other glycosaminoglycans in EC permeability is a question of great interest. The dimensions of total glycocalyx (BSA) and the HS subcomponent measured were within the range of previously reported values for rodent cell cultures and animal models using the same fixation and microscopy approach.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, previously published studies did not attempt to repair the glycocalyx, but only compared the healthy glycocalyx to the degraded glycocalyx. 18,23,34 Hence, exogenous HS was added back into the culture after HS degradation, in the hopes of observing a change in PEG-AuNP uptake from the degraded model.…”

Section: Resultsmentioning

confidence: 99%

“…Unfortunately, the glycocalyx is generally not properly modeled in the development of NPbased therapeutic approaches and can lead to incorrect uptake and permeability measurements in vitro. 18,19,28 Additionally, ECs are not the only cell type to express glycocalyx -most other mammalian cells as well as circulating cancer cells also express unique glycocalyx. 18,19,28,33,35 Therefore, elucidating the role the glycocalyx plays in the cellular uptake of NPs by ECs will benefit the field of nanomedicine and drug delivery for cardiovascular and other diseases.…”

Section: Introductionmentioning

confidence: 99%

“…1,[9][10][11][12] Vascular disease progression, such as atherosclerotic vessel hardening or lipid-and macrophage-filled plaque formation, is facilitated by EC dysfunction 13 and coincides with shedding of the EC glycocalyx coat. [14][15][16][17] Furthermore, a compromised glycocalyx has been shown to increase the permeability of nanoscale particles in other cell types such as erythrocytes 18 and cancer tumor cells. 19 Therefore, a potential avenue for treating vascular diseases is to target ECs and their glycocalyx, rather than simply utilizing the systemic and medicinal treatments that are common today.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Cheng¹,

Kumar²,

Sridhar³

et al. 2016

IJN

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Cheng¹,

Kumar²,

Sridhar³

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

Materials for Cell Surface Engineering

et al. 2023

View full text Add to dashboard Cite

Cell therapies are emerging as a promising new therapeutic modality in medicine, generating effective treatments for previously incurable diseases. Clinical success of cell therapies has energized the field of cellular engineering, spurring further exploration of novel approaches to improve their therapeutic performance. Engineering of cell surfaces using natural and synthetic materials has emerged as a valuable tool in this endeavor. This review summarizes recent advances in the development of technologies for decorating cell surfaces with various materials including nanoparticles, microparticles, and polymeric coatings, focusing on the ways in which surface decorations enhance carrier cells and therapeutic effects. Key benefits of surface‐modified cells include protecting the carrier cell, reducing particle clearance, enhancing cell trafficking, masking cell‐surface antigens, modulating inflammatory phenotype of carrier cells, and delivering therapeutic agents to target tissues. While most of these technologies are still in the proof‐of‐concept stage, the promising therapeutic efficacy of these constructs from in vitro and in vivo preclinical studies has laid a strong foundation for eventual clinical translation. Cell surface engineering with materials can imbue a diverse range of advantages for cell therapy, creating opportunities for innovative functionalities, for improved therapeutic efficacy, and transforming the fundamental and translational landscape of cell therapies.

show abstract

A Safe and Efficient Strategy for the Rapid Elimination of Blood Lead In Vivo Based on a Capture–Fix–Separate Mechanism

Wan

Chi

et al. 2019

Angewandte Chemie

View full text Add to dashboard Cite

Lead poisoning is an important problem because of its serious effects on human health. Yetasolution is not available due to an incomplete understanding of the state of lead ions in blood. Since most blood lead binds to hemoglobin (Hb) in red blood cells,i dentifying and capturing leadcontaminated Hb in RBCs is important. Herein, am agnetic blood lead remover with hyperbranched poly(amidoamine)s (HPAM) as template/co-adsorbent and core-shell mesoporous structure was synthesized. Lead-containing Hb was selectively captured and then fixedb ym esoporous channels. The magnetic separation technology was used to separate the magnetic remover from blood. Ar elated blood lead clean-up apparatus was used to remove lead from the blood of ap ig in vivo.R esults of physical/chemical characterizations,b iocompatibility experiments,a nimal tests,a nd theoretical simulation verify the safety and efficiency of this removal strategy and the high efficiency of the blood lead clean-up apparatus.

show abstract

Influence of the glycocalyx and plasma membrane composition on amphiphilic gold nanoparticle association with erythrocytes

Cited by 51 publications

References 66 publications

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Materials for Cell Surface Engineering

A Safe and Efficient Strategy for the Rapid Elimination of Blood Lead In Vivo Based on a Capture–Fix–Separate Mechanism

Contact Info

Product

Resources

About