Surface-associated serum proteins inhibit the uptake of phosphatidylserine and poly(ethylene glycol) liposomes by mouse macrophages

Johnstone, Sharon A.; Masin, Dana; Mayer, Lawrence D.; Bally, Marcel B.

doi:10.1016/s0005-2736(01)00292-9

Cited by 115 publications

(85 citation statements)

References 59 publications

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“…In a typical experimental plan, NPs are incubated in a biological fluid that ideally should replicate the features of the in vivo biological milieu. After incubation, the NPs are recovered by centrifugation, ultrafiltration [60,65] or, more recently, by a combination of size exclusion chromatography and ultrafiltration [66], and extensively washed to avoid contamination of nonbound proteins. Finally, the adsorbed proteins are eluted from the NP surface and analyzed by two different methods: gel-based or gel-free proteomics [67].…”

Section: New Modelmentioning

confidence: 99%

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

Corbo

Molinaro

Parodi

et al. 2015

Nanomedicine (Lond.)

537

443

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In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP–PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.

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Section: New Modelmentioning

confidence: 99%

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

Corbo

Molinaro

Parodi

et al. 2015

Nanomedicine (Lond.)

537

443

View full text Add to dashboard Cite

show abstract

“…16,25,26) our results in vitro indicated that increasing FALT did not necessarily prevent doX uptake by Ehrlich ascites carcinoma cells. The intracellular level of doX was different in the liposomes, the order of doX uptake by cells after 30 min incubation being PEG-unmodified liposomal doX= SL2000= SL(2000 : 500= 2 : 1)>SL500, thus the level of cell uptake was affected by the kind of PEG modification of liposomes.…”

Section: Effect Of Mixed Peg-modified Liposomal Doxorubicinmentioning

confidence: 69%

Change in the Character of Liposomes as a Drug Carrier by Modifying Various Polyethyleneglycol-Lipids

Sugiyama

Sadzuka

2013

Biological & Pharmaceutical Bulletin

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When liposomes, as a superior drug carrier, are injected intravenously, active liposomes as medicines require polyethyleneglycol (PEG) as a modification tool around the liposomal membrane. PEG modification of a liposome forms a fixed aqueous layer, and the trapping by cells of the reticuloendothelial system (RES) is avoided. Hence, PEG-modified liposomes have long circulation in the bloodstream, and passive targeting to tumors has been achieved by PEG modification. We have been studying the passive targeting by liposomes with the expectation of more usefulness. It was proved a correlation between the PEG molecular weight of PEG-modified liposomes and blood circulation time and antitumor effect, too. Liposomes modified by PEG2000 were useful for uptake into tumor cells. We thought that the re-uptake in the liposomal membrane also increased accumulation. Moreover, it was proved that mixing two different PEGs to modify the liposome surface gives a bigger fixed aqueous layer thickness (FALT) around the liposome, giving the liposome strong antitumor activity. Then, we designed a novel PEG-lipid, 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-PEG (different double arms PEG; DDA-PEG), which had two different PEGs (2000 and 500) in one molecule. One of the innovative characteristics of DDA-PEG-modified liposome (DDAL) is that it heightens the contact ability with tumor cells. DDAL may be an effective DDS carrier for solving various PEG dilemmas. It was observed that passive targeting by PEG-modified liposomes had different characteristics by changing PEG length, anchor type or those combination. Thus, it should be applied to liposomes suitable for various diseases.

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“…20,21 As shown in Figure 2, the cellular uptake efficiencies of both GGLG and M-GGLG liposomes largely declined as a result of serum inhibition in HeLa, HCC1954, MDA-MB-468, and COS-7 cells. The cellular uptake of GGLG liposomes was decreased to 22%-28% of that in serum-free medium.…”

Section: Influence Of Serum On the Cellular Uptake Of Liposomesmentioning

confidence: 96%

Enhanced cellular uptake of maleimide-modified liposomes via thiol-mediated transport

Li¹,

Takeoka²

2014

IJN

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With a small amount of maleimide modification on the liposome surface, enhanced cellular uptake of liposomes and drug-delivery efficiency can be obtained both in vitro and in vivo. Herein, we describe the mechanisms underlying this enhanced cellular uptake. Suppression of the cellular uptake of maleimide-modified liposomes (M-GGLG, composed of 1,5-dihexadecyl N,N -diglutamyl-lysyl-L-glutamate [GGLG]/cholesterol/poly(ethylene glycol) – 1,2-distearoyl- sn -glycero-3-phosphoethanolamine [PEG 5000 -DSPE]/maleimide [M]-PEG 5000 -Glu2C 18 at a molar ratio of 5:5:0.03:0.03) caused by temperature block and addition of serum was alleviated compared with that of liposomes without maleimide modification (GGLG liposomes, composed of GGLG/cholesterol/PEG 5000 -DSPE/PEG 5000 -Glu2C 18 at a molar ratio of 5:5:0.03:0.03). When 0.01 nM N -ethylmaleimide was used to pre-block cellular thiols, the cellular uptake of M-GGLG liposomes was decreased to approximately 70% in HeLa, HCC1954, MDA-MB-468, and COS-7 cell lines. Moreover, inhibition of a thiol-related reductase such as protein disulfide isomerase resulted in a 15%–45% inhibition of the cellular uptake of M-GGLG liposomes, whereas GGLG liposomes were not influenced. Further, single and mixed inhibitors of clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis did not efficiently inhibit the cellular uptake of M-GGLG liposomes. Using confocal microscopy, we verified that M-GGLG liposomes were localized partially in lysosomes after inhibition of the mentioned conventional endocytic pathways. Therefore, it was hypothesized that the mechanisms underlying the enhanced cellular uptake of liposomes by maleimide modification was thiol-mediated membrane trafficking, including endocytosis and energy-independent transport.

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Surface-associated serum proteins inhibit the uptake of phosphatidylserine and poly(ethylene glycol) liposomes by mouse macrophages

Cited by 115 publications

References 59 publications

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

Change in the Character of Liposomes as a Drug Carrier by Modifying Various Polyethyleneglycol-Lipids

Enhanced cellular uptake of maleimide-modified liposomes via thiol-mediated transport

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