Chemical Reactive Anchoring Lipids with Different Performance for Cell Surface Re-engineering Application

Vabbilisetty, Pratima; Boron, Mallorie; Nie, Huan; Ozhegov, Evgeny; Sun, Xue‐Long

doi:10.1021/acsomega.7b01886

Cited by 24 publications

(17 citation statements)

References 30 publications

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“…Various techniques have been developed to modify or engineer cell surface and liposomes. For examples, chemical reactive anchor lipids, phosphatidylethanolamine-poly-(ethylene glycol)dibenzocyclooctyne and cholesterol-PEG-dibenzocyclooctyne, have been synthesized to study the structure, function and molecular mechanism of cell surface molecules [48] . Cell lipid membrane has been modified with poly(ethylene glycol)-conjugated phospholipids with uniform distribution [49] .…”

Section: Advanced Surface Tagging Technologymentioning

confidence: 99%

Targeted Exosomes for Drug Delivery: Biomanufacturing, Surface Tagging, and Validation

Kim

Zhang

et al. 2019

Biotechnology Journal

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Exosomes hold great potential to deliver therapeutic reagents for cancer treatment due to its inherent low antigenicity. However, several technical barriers need be overcome before widely clinical applications, such as low productivity and ineffective cancer targeting. The present study aimed at creating a new biomanufacturing platform of cancer-targeted exosomes for drugs delivery.Specifically, we created a scalable, robust, high-yield, cell line-based exosomes production process in stirred-tank bioreactor, and developed an efficient surface tagging technique to generate mAbexosomes. The in vitro characterization using transmission electron microscopy, NanoSight nanoparticle tracking analysis and Western blotting confirmed the high quality of exosomes. Flow cytometry and confocal laser scanning microscopy imaging demonstrated mAb-exosomes had strong surface binding to cancer cells. Furthermore, to validate the targeted drug delivery efficiency, we loaded Romidepsin, a histone deacetylase inhibitor, into mAb-exosomes. The in vitro anti-cancer toxicity study showed high cytotoxicity of mAb-exosome-Romidepsin to cancer cells. Finally, the in vivo study using tumor xenograft animal model validated the cancer targeting specificity, anti-cancer efficacy, and drug delivery capability of the targeted exosomes. In summary, we developed new techniques enabling targeted exosomes for drug delivery to support large-scale animal studies and facilitate the translation from research to clinics.

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Section: Advanced Surface Tagging Technologymentioning

confidence: 99%

Targeted Exosomes for Drug Delivery: Biomanufacturing, Surface Tagging, and Validation

Kim

Zhang

et al. 2019

Biotechnology Journal

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“…Specifically, cholesterol was used for its ability to intercalate into lipid rafts (Karp & Zhao, 2014; Simons & Ikonen, 2000). Sun et al showed cholesterol‐PEG can be used to modify 99% of cells in a population (Vabbilisetty, Boron, Nie, Ozhegov, & Sun, 2018). As a result, we hypothesized that lipid insertion would allow for modification of a higher fraction of cells than covalent methods.…”

Section: Introductionmentioning

confidence: 99%

Increased yield of gelatin coated therapeutic cells through cholesterol insertion

Davis

Peng

Chelvarajan

et al. 2020

J Biomedical Materials Res

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Gelatin coatings are effective in increasing the retention of MSCs injected into the heart and minimizing the damage from acute myocardial infarction (AMI), but early studies suffered from low fractions of the MSCs coated with gelatin. Biotinylation of the MSC surface is a critical first step in the gelatin coating process, and in this study, we evaluated the use of biotinylated cholesterol “lipid insertion” anchors as a substitute for the covalent NHS‐biotin anchors to the cell surface. Streptavidin‐eosin molecules, where eosin is our photoinitiator, can then be bound to the cell surface through biotin‐streptavidin affinity. The use of cholesterol anchors increased streptavidin density on the surface of MSCs further driving polymerization and allowing for an increased fraction of MSCs coated with gelatin (83%) when compared to NHS‐biotin (52%). Additionally, the cholesterol anchors increased the uniformity of the coating on the MSC surface and supported greater numbers of coated MSCs even when the streptavidin density was slightly lower than that of an NHS‐biotin anchoring strategy. Critically, this improvement in gelatin coating efficiency did not impact cytokine secretion and other critical MSC functions. Proper selection of the cholesterol anchor and the biotinylation conditions supports cellular function and densities of streptavidin on the MSC surface of up to ~105 streptavidin molecules/μm2. In all, these cholesterol anchors offer an effective path towards the formation of conformal coatings on the majority of MSCs to improve the retention of MSCs in the heart following AMI.

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“…Currently, there are three categories of modification strategies: (1) hydrophobic interaction, (2) covalent conjugation, and (3) electrostatic interaction. Lipid-PEG has attracted much attention for its ability to form a uniform ultrathin coating on the surface of cells without covalent bonds or electrostatic interactions, either one of which can lead to severe cytotoxicity [14].…”

Section: Introductionmentioning

confidence: 99%

DMPE-PEG scaffold binding with TGF-β1 receptor enhances cardiomyogenic differentiation of adipose-derived stem cells

2018

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BackgroundHeart failure has become a global health problem with increasing incidences worldwide. Traditional pharmacological treatments can delay but cannot reverse the underlying disease processes. The clinical application of myocardial tissue engineering represents a promising strategy because it features cell-based replacement therapies that replace partially or fully damaged cardiac tissues with in vitro-generated tissue equivalents. However, the effectiveness of this therapy is limited by poor viability and differentiation of the grafted cells. This limitation could be overcome by rapidly increasing the numbers of functional cardiomyocytes. In this study, we aimed to obtain functional myocardial tissue engineering seed cells with high proliferation and differentiation rates by combining 1,2-dimyristoyl-sn-glycero-3-phosphoethan-olamine-polyethylene glycol (DMPE-PEG) and recombinant transforming growth factor-β1 receptor I (rTGF-β1 RI), followed by binding to human adipose-derived stromal cells (hADSCs).MethodsTo induce higher expression level of TGF-β1 RI, DMPE-PEG was inoculated with rTGF-β1 RI to modify the surface of hADSCs. The differentiation ability and morphological characteristics of the modified hADSCs were examined in vitro and in vivo.ResultsThe caridiomyocartic differentiation ability of TGF-β1 RI-modified hADSCs was significantly enhanced, as indicated by elevated expression levels of the cardiac markers cardiac troponin T (cTnT) and α-smooth muscle actin (SMA) via increased phosphorylation of the Smad signaling pathway-related proteins.ConclusionOur findings provide new insights into stem cell transplantation therapy in myocardial tissue engineering.

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Chemical Reactive Anchoring Lipids with Different Performance for Cell Surface Re-engineering Application

Cited by 24 publications

References 30 publications

Targeted Exosomes for Drug Delivery: Biomanufacturing, Surface Tagging, and Validation

Targeted Exosomes for Drug Delivery: Biomanufacturing, Surface Tagging, and Validation

Increased yield of gelatin coated therapeutic cells through cholesterol insertion

DMPE-PEG scaffold binding with TGF-β1 receptor enhances cardiomyogenic differentiation of adipose-derived stem cells

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