Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity

Torchilin, Vladimir P.; Omelyanenko, V.; Papisov, Mikhail; Bogdanov, Alexei A.; Trubetskoy, Vladimir S.; Herron, James N.; Gentry, Christine

doi:10.1016/0005-2736(94)90003-5

Cited by 454 publications

(224 citation statements)

References 20 publications

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“…For clinical use, and especially in the cancer field, these liposomes are around 100 nm in size and are coated with polyethylene glycol (PEG), which prevents opsonization and recognition by macrophages and further increases circulation time. [14][15][16] Because of liposome size and their capacity to remain in the blood, passive accumulation in tumors is observed, which is believed to result from leaky and permeable vessels in tumors, and is also designated enhanced permeability and retention effect. 17 Modified PEGylated liposomes can be further used to target antigens by decorating the liposome surface with antibodies, [18][19][20] which results in increased accumulation in tumor cells as compared to healthy tissue.…”

Section: Introductionmentioning

confidence: 99%

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Saeed

Brakel

Zalba

et al. 2016

IJN

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Therapy of melanoma using T-cells with genetically introduced T-cell receptors (TCRs) directed against a tumor-selective cancer testis antigen (CTA) NY-ESO1 demonstrated clear antitumor responses in patients without side effects. Here, we exploited the concept of TCR-mediated targeting through introduction of single-chain variable fragment (scFv) antibodies that mimic TCRs in binding major histocompatibility complex-restricted CTA. We produced scFv antibodies directed against Melanoma AntiGEn A1 (MAGE A1) presented by human leukocyte antigen A1 (HLA-A1), in short M1/A1, and coupled these TCR-like antibodies to liposomes to achieve specific melanoma targeting. Two anti-M1/A1 antibodies with different ligand-binding affinities were derived from a phage-display library and reformatted into scFvs with an added cysteine at their carboxyl termini. Protein production conditions, ie, bacterial strain, temperature, time, and compartments, were optimized, and following production, scFv proteins were purified by immobilized metal ion affinity chromatography. Batches of pure scFvs were validated for specific binding to M1/A1-positive B-cells by flow cytometry. Coupling of scFvs to liposomes was conducted by employing different conditions, and an optimized procedure was achieved. In vitro experiments with immunoliposomes demonstrated binding of M1/A1-positive B-cells as well as M1/A1-positive melanoma cells and internalization by these cells using flow cytometry and confocal microscopy. Notably, the scFv with nonenhanced affinity of M1/A1, but not the one with enhanced affinity, was exclusively bound to and internalized by melanoma tumor cells expressing M1/A1. Taken together, antigen-mediated targeting of tumor cells as well as promoting internalization of nanoparticles by these tumor cells is mediated by TCR-like scFv and can contribute to melanoma-specific targeting.

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Section: Introductionmentioning

confidence: 99%

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Saeed

Brakel

Zalba

et al. 2016

IJN

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“…[20][21][22] As a result, it is considered that PEG-modified liposomes have a long circulation time. 8,9) However, the amount of PEG-lipids inserted into the liposome membranes is limited, and FALT forming around the liposomes reaches a plateau, 23) so it was considered that increasing FALT was difficult. Then, we tried mixing two different PEGs to modify the liposome surface for the purpose of increasing FALT and avoiding trapping by RES.…”

Section: Mixing Two Different Pegs Tomentioning

confidence: 99%

“…And prolongation of liposome circulation in the bloodstream and passive targeting to tumor has been achieved by PEG modification of the liposome surface. [4][5][6][7][8][9][10][11] Furthermore, PEG modification around liposomes gives high stability: about a few years at room temperature, high blood circulation, and longer blood half time. In the case of using PEG as a liposome modifying material, PEG should have a hydrophobic anchor for interaction with phospholipids of a liposomal membrane.…”

Section: Introductionmentioning

confidence: 99%

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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“…However, the drawback of PEGylation is limited uptake in targeted cells and hindering of endosomal escape following uptake. 16,17 To solve this PEGylation dilemma, different strategies have been reported for triggered dePEGylation at the target site. Examples are conjugation of PEG to the nanoparticle through labile linkers, such as disulfide bonds, 18 pH-sensitive groups, 19 or esterasesensitive groups.…”

Section: Introductionmentioning

confidence: 99%

Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells

Bruun¹,

Larsen²,

Jølck³

et al. 2015

IJN

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Clinical applications of siRNA for treating disorders in the central nervous system require development of systemic stable, safe, and effective delivery vehicles that are able to cross the impermeable blood–brain barrier (BBB). Engineering nanocarriers with low cellular interaction during systemic circulation, but with high uptake in targeted cells, is a great challenge and is further complicated by the BBB. As a first step in obtaining such a delivery system, this study aims at designing a lipid nanoparticle (LNP) able to efficiently encapsulate siRNA by a combination of titratable cationic lipids. The targeted delivery is obtained through the design of a two-stage system where the first step is conjugation of angiopep to the surface of the LNP for targeting the low-density lipoprotein receptor-related protein-1 expressed on the BBB. Second, the positively charged LNPs are masked with a negatively charged PEGylated (poly(ethylene glycol)) cleavable lipopeptide, which contains a recognition sequence for matrix metalloproteinases (MMPs), a class of enzymes often expressed in the tumor microenvironment and inflammatory BBB conditions. Proteolytic cleavage induces PEG release, including the release of four glutamic acid residues, providing a charge switch that triggers a shift of the LNP charge from weakly negative to positive, thus favoring cellular endocytosis and release of siRNA for high silencing efficiency. This work describes the development of this two-stage nanocarrier-system and evaluates the performance in brain endothelial and glioblastoma cells with respect to uptake and gene silencing efficiency. The ability of activation by MMP-triggered dePEGylation and charge shift is demonstrated to substantially increase the uptake and the silencing efficiency of the LNPs.

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Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity

Cited by 454 publications

References 20 publications

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

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

Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells

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Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity

Cited by 454 publications

References 20 publications

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

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

Investigation of enzyme-sensitive lipid&nbsp;nanoparticles for delivery of siRNA to blood&ndash;brain barrier and glioma cells

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Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells