Preparation of Biointeractive Glycoprotein-Conjugated Hydrogels through Metabolic Oligosacchalide Engineering

Iwasaki, Yasuhiko; Matsunaga, Aki; Fujii, Shuetsu

doi:10.1021/bc5003295

Cited by 11 publications

(10 citation statements)

References 39 publications

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“…These moieties are reactive and can be modified at the cell surface with little or no side reactions using bio-orthogonal chemistry 154. This approach has been used to modify cells for drug conjugation,155 selective killing of cells,154 surface-induced gelation156 and artificial adhesion to 2D substrates151 or 3D scaffolds 152. To date, bio-orthogonal chemistry has only been used in proof-of-principle experiments to introduce simple proteins and fluorophores to azide-modified EVs 153.…”

Section: Engineering Extracellular Vesicles Via Cell Modificationmentioning

confidence: 99%

Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics

2017

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In the last decade, extracellular vesicles (EVs) have emerged as a key cell-free strategy for the treatment of a range of pathologies, including cancer, myocardial infarction and inflammatory diseases. Indeed, the field is rapidly transitioning from promising in vitro reports towards in vivo animal models and early clinical studies. These investigations exploit the high physicochemical stability and biocompatibility of EVs, as well as their innate capacity to communicate with cells over long distances via signal transduction and membrane fusion. This review will focus on methods in which EVs can be chemically or biologically modified to broaden, alter or enhance their therapeutic capability. We will examine two broad strategies, which have been used to introduce a wide range of nanoparticles, reporter systems, targeting peptides, pharmaceutics and functional RNA molecules. First, we will explore how EVs can be modified by manipulating their parent cells; either through genetic or metabolic engineering, or by introducing exogenous material that is subsequently incorporated into secreted EVs. Second, we consider how EVs can be directly functionalized using strategies such as hydrophobic insertion, covalent surface chemistry and membrane permeabilization. We will discuss the historical context of each specific technology, present prominent examples and evaluate the complexities, potential pitfalls and opportunities presented by different re-engineering strategies. KeywordsExtracellular Vesicles; Exosomes; Microvesicles; Functionalization; Genetic Manipulation; Drug Loading; Membrane Modification; Cell-Free Therapy Extracellular Vesicles: Cell-Derived Nanovectors Extracellular vesicles (EVs) are a collective of small, naturally-derived particles, which, until recently, represented an overlooked and underappreciated component of the cellular secretome. Three major categories of EV have been defined, predominantly based upon vesicle biogenesis, but with notable differences in size and composition.1,2 Exosomes are formed when the peripheral membrane of multivesicular bodies (MVBs) undergo reverse budding to form small nanovesicles (30-100 nm in diameter) that are released when MVBs fuse with the cytoplasmic membrane.3 Microvesicles are larger in size (c.f. 100-1000 nm) * m.stevens@imperial.ac.uk. Europe PMC Funders GroupAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2017 September 19.Published in final edited form as: ACS Nano. 2017 January 24; 11(1): 69-83. doi:10.1021/acsnano.6b07607. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts and are produced during shedding or budding of the cytoplasmic membrane.4 Exosomes and microvesicles are produced by healthy cells as part of regular membrane turnover and exocytosis. In contrast, apoptotic bodies (c.f. 500-2000 nm) are generated from outward membrane blebbing in cells undergoing apoptosis.5 Apoptotic bodies, microvesicles and exosomes are each enclosed by a phospholipid membrane bilayer, comparable to the cytoplasmic mem...

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Section: Engineering Extracellular Vesicles Via Cell Modificationmentioning

confidence: 99%

Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics

2017

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“… 538 , 539 However, in a notable example Iwasaki et al demonstrated that the subsequent isolation of modified glycoproteins bearing methacrylated sialic acid motifs could be used to functionalize hydrogel scaffolds. 540 …”

Section: Incorporating Reactive Handlesmentioning

confidence: 99%

Achieving Controlled Biomolecule–Biomaterial Conjugation

2018

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The conjugation of biomolecules can impart materials with the bioactivity necessary to modulate specific cell behaviors. While the biological roles of particular polypeptide, oligonucleotide, and glycan structures have been extensively reviewed, along with the influence of attachment on material structure and function, the key role played by the conjugation strategy in determining activity is often overlooked. In this review, we focus on the chemistry of biomolecule conjugation and provide a comprehensive overview of the key strategies for achieving controlled biomaterial functionalization. No universal method exists to provide optimal attachment, and here we will discuss both the relative advantages and disadvantages of each technique. In doing so, we highlight the importance of carefully considering the impact and suitability of a particular technique during biomaterial design.

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“…[ 37,62,63 ] On the other end, introduction of bio‐orthogonal functionalities at the cell membrane offers clear advantages over nonspecific polymer conjugation, including better cytocompatibility and stability of conjugation. [ 64–66 ] The cell surface repertoire can be expanded to include abiotic functionality through the biosynthetic introduction of unnatural sugars into cellular glycans, a process termed metabolic oligosaccharide engineering (MOE). [ 13,67,68 ] This method was pioneered by Bertozzi and co‐workers and allows easy incorporation of bio‐orthogonal handles in vitro and in vivo.…”

Section: Covalent Conjugation Using Bio‐orthogonal Chemistrymentioning

confidence: 99%

Engineering the Mammalian Cell Surface with Synthetic Polymers: Strategies and Applications

Arno

2020

Macromol. Rapid Commun.

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Manipulating the surface of living cells represents a powerful tool by which to control cell behavior and provides a unique strategy to modulate cellular function and cell–cell interactions. Recent progress in this area has seen the development of robust and elegant approaches to selectively decorate the cell surface, leading to unprecedented advances in cellular manipulation and cell‐based therapies. Despite some impressive in vitro results, several obstacles remain to the broader application of some of these strategies, including their limited translation in vivo. In this review, the leading techniques used to introduce polymers at the plasma membrane of mammalian cells are discussed, focusing on strategies that generate a stable and homogeneous distribution of polymeric chains at the cell surface. Application of these strategies to control cell behavior and deliver cell‐based therapies to targeted tissues are highlighted.

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Preparation of Biointeractive Glycoprotein-Conjugated Hydrogels through Metabolic Oligosacchalide Engineering

Cited by 11 publications

References 39 publications

Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics

Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics

Achieving Controlled Biomolecule–Biomaterial Conjugation

Engineering the Mammalian Cell Surface with Synthetic Polymers: Strategies and Applications

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