Dataset Information

Fluorescent Magnetopolymersomes: A Theranostic Platform to Track Intracellular Delivery.

ABSTRACT: We present a potential theranostic delivery platform based on the amphiphilic diblock copolymer polybutadiene-block-poly (ethylene oxide) combining covalent fluorescent labeling and membrane incorporation of superparamagnetic iron oxide nanoparticles for multimodal imaging. A simple self-assembly and labeling approach to create the fluorescent and magnetic vesicles is described. Cell uptake of the densely PEGylated polymer vesicles could be altered by surface modifications that vary surface charge and accessibility of the membrane active species. Cell uptake and cytotoxicity were evaluated by confocal microscopy, transmission electron microscopy, iron content and metabolic assays, utilizing multimodal tracking of membrane fluorophores and nanoparticles. Cationic functionalization of vesicles promoted endocytotic uptake. In particular, incorporation of cationic lipids in the polymersome membrane yielded tremendously increased uptake of polymersomes and magnetopolymersomes without increase in cytotoxicity. Ultrastructure investigations showed that cationic magnetopolymersomes disintegrated upon hydrolysis, including the dissolution of incorporated iron oxide nanoparticles. The presented platform could find future use in theranostic multimodal imaging in vivo and magnetically triggered delivery by incorporation of thermorepsonsive amphiphiles that can break the membrane integrity upon magnetic heating via the embedded superparamagnetic nanoparticles.

SUBMITTER: Bixner O

PROVIDER: S-EPMC5706250 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Fluorescent Magnetopolymersomes: A Theranostic Platform to Track Intracellular Delivery.

Bixner Oliver O Gal Noga N Zaba Christoph C Scheberl Andrea A Reimhult Erik E

Materials (Basel, Switzerland) 20171113 11

We present a potential theranostic delivery platform based on the amphiphilic diblock copolymer polybutadiene-<i>block</i>-poly (ethylene oxide) combining covalent fluorescent labeling and membrane incorporation of superparamagnetic iron oxide nanoparticles for multimodal imaging. A simple self-assembly and labeling approach to create the fluorescent and magnetic vesicles is described. Cell uptake of the densely PEGylated polymer vesicles could be altered by surface modifications that vary surfa ...[more]

PMID: 29137172

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Project description:BackgroundNanoinjection-the process of intracellular delivery using vertically configured nanostructures-is a physical route that efficiently negotiates the plasma membrane, with minimal perturbation and toxicity to the cells. Nanoinjection, as a physical membrane-disruption-mediated approach, overcomes challenges associated with conventional carrier-mediated approaches such as safety issues (with viral carriers), genotoxicity, limited packaging capacity, low levels of endosomal escape, and poor versatility for cell and cargo types. Yet, despite the implementation of nanoinjection tools and their assisted analogues in diverse cellular manipulations, there are still substantial challenges in harnessing these platforms to gain access into cell interiors with much greater precision without damaging the cell's intricate structure. Here, we propose a non-viral, low-voltage, and reusable electroactive nanoinjection (ENI) platform based on vertically configured conductive nanotubes (NTs) that allows for rapid influx of targeted biomolecular cargos into the intracellular environment, and for successful gene silencing. The localization of electric fields at the tight interface between conductive NTs and the cell membrane drastically lowers the voltage required for cargo delivery into the cells, from kilovolts (for bulk electroporation) to only ≤ 10 V; this enhances the fine control over membrane disruption and mitigates the problem of high cell mortality experienced by conventional electroporation.ResultsThrough both theoretical simulations and experiments, we demonstrate the capability of the ENI platform to locally perforate GPE-86 mouse fibroblast cells and efficiently inject a diverse range of membrane-impermeable biomolecules with efficacy of 62.5% (antibody), 55.5% (mRNA), and 51.8% (plasmid DNA), with minimal impact on cells' viability post nanoscale-EP (> 90%). We also show gene silencing through the delivery of siRNA that targets TRIOBP, yielding gene knockdown efficiency of 41.3%.ConclusionsWe anticipate that our non-viral and low-voltage ENI platform is set to offer a new safe path to intracellular delivery with broader selection of cargo and cell types, and will open opportunities for advanced ex vivo cell engineering and gene silencing.

Dataset Information

Fluorescent Magnetopolymersomes: A Theranostic Platform to Track Intracellular Delivery.

Publications

Fluorescent Magnetopolymersomes: A Theranostic Platform to Track Intracellular Delivery.

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