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Biomimetic artificial organelles with in vitro and in vivo activity triggered by reduction in microenvironment

Einfalt, Tomaz and Witzigmann, Dominik and Edlinger, Christoph and Sieber, Sandro and Goers, Roland and Najer, Adrian and Spulber, Mariana and Onaca-Fischer, Ozana and Huwyler, Jörg and Palivan, Cornelia G.. (2018) Biomimetic artificial organelles with in vitro and in vivo activity triggered by reduction in microenvironment. Nature Communications, 9. p. 1127.

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Official URL: https://edoc.unibas.ch/62335/

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Abstract

Despite tremendous efforts to develop stimuli-responsive enzyme delivery systems, their efficacy has been mostly limited to in vitro applications. Here we introduce, by using an approach of combining biomolecules with artificial compartments, a biomimetic strategy to create artificial organelles (AOs) as cellular implants, with endogenous stimuli-triggered enzymatic activity. AOs are produced by inserting protein gates in the membrane of polymersomes containing horseradish peroxidase enzymes selected as a model for natures own enzymes involved in the redox homoeostasis. The inserted protein gates are engineered by attaching molecular caps to genetically modified channel porins in order to induce redox-responsive control of the molecular flow through the membrane. AOs preserve their structure and are activated by intracellular glutathione levels in vitro. Importantly, our biomimetic AOs are functional in vivo in zebrafish embryos, which demonstrates the feasibility of using AOs as cellular implants in living organisms. This opens new perspectives for patient-oriented protein therapy.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Einfalt, Tomaz and Witzigmann, Dominik and Sieber, Sandro and Fischer, Ozana Simina and Palivan, Cornelia G and Goers, Roland
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:13 Jun 2018 09:08
Deposited On:09 Apr 2018 12:14

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