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ANTIOXIDANT NANOREACTORS BASED ON CO-ENCAPSULATION OF ENZYMES IN POLYMERIC VESICLES

English title ANTIOXIDANT NANOREACTORS BASED ON CO-ENCAPSULATION OF ENZYMES IN POLYMERIC VESICLES
Applicant Palivan Cornelia
Number 124406
Funding scheme Project funding
Research institution Physikalische Chemie Departement Chemie Universität Basel
Institution of higher education University of Basel - BS
Main discipline Physical Chemistry
Start/End 01.06.2009 - 31.05.2012
Approved amount 195'775.00
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Keywords (11)

superoxide dismutase (SOD); triblock copolymers; self-assembly; antioxidant nanoreactor; catalase; horseradish peroxidase (HRP); nanovesicles; nanoreactor; Cu/Zn-superoxide dismutase; amphiphilic copolymers; superoxide anions

Lay Summary (English)

Lead
Lay summary
Introduction: Nanoreactors based on encapsulation of active compounds in polymeric carriers where they are able to act in situ have recently been developed as a new alternative to the conventional systems in use in various domains, such as catalysis or therapeutics. Amphiphilic block copolymers that auto-assemble in dilute solutions and form various architectures, as for example vesicles, represent efficient systems to design new nanoreactors, in combination with reactive molecules acting inside. Similar to liposomes from the point of view of molecule encapsulation, polymer nanovesicles are by far more stable and offer a better control of their properties, making them the preferred option for technological applications.Objective: The present study aims to design and test antioxidant nanoreactors based on the encapsulation of Cu/Zn-SOD, a known antioxidant enzyme or a tandem of SOD and a second enzyme such as Catalase for an efficient detoxification of superoxide radicals, known to be involved in oxidative stress in vivo. Research plan: 1. We will develop an antioxidant nanoreactor by encapsulating Cu/Zn-SOD in amphiphilic copolymer nanovesicles whose membrane is oxygen permeable. By changing the copolymer molecular properties, such as nature or length of the polymer blocks and hydrophobic-hydrophilic ratio, various constraints will be imposed on the protein in order to see if its active site is affected by its location inside vesicles, and to improve the effectiveness of the nanoreactor. 2. Cu/Zn-SOD will be co-encapsulated in polymeric nanocontainers together with an additional enzyme acting in a cascade reaction to allow a complete detoxification of superoxide radicals, with water as the final product. Advantages:The design of an antioxidant nanoreactor based on encapsulation/co-encapsulation of enzymes acting in tandem represents a new direction for developing drug delivery applications which avoids the disadvantages of conventional drug release systems.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
Polymeric nanocarriers and nanoreactors: a survey of possible therapeutic applications.
Onaca-Fischer Ozana, Liu Juan, Inglin Mark, Palivan Cornelia G (2012), Polymeric nanocarriers and nanoreactors: a survey of possible therapeutic applications., in Current pharmaceutical design, 18(18), 2622-43.
Mimicking the cell membrane with block copolymer membranes
Zhang XY, Tanner P, Graff A, Palivan CG, Meier W (2012), Mimicking the cell membrane with block copolymer membranes, in JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 50(12), 2293-2318.
Protein-polymer nanoreactors for medical applications.
Palivan Cornelia G, Fischer-Onaca Ozana, Delcea Mihaela, Itel Fabian, Meier Wolfgang (2012), Protein-polymer nanoreactors for medical applications., in Chemical Society reviews, 41(7), 2800-23.
Stimuli-responsive polymers and their applications in nanomedicine.
Cabane Etienne, Zhang Xiaoyan, Langowska Karolina, Palivan Cornelia G, Meier Wolfgang (2011), Stimuli-responsive polymers and their applications in nanomedicine., in Biointerphases, 7(1-4), 9-9.
Polymeric vesicles: from drug carriers to nanoreactors and artificial organelles.
Tanner Pascal, Baumann Patric, Enea Ramona, Onaca Ozana, Palivan Cornelia, Meier Wolfgang (2011), Polymeric vesicles: from drug carriers to nanoreactors and artificial organelles., in Accounts of chemical research, 44(10), 1039-49.
Photoresponsive Polymersomes as Smart Triggerable Nanocarriers
Cabane Etienne, Malinova Violeta, Menon Shindu, Palivan Cornelia, Meier Wolfgang (2011), Photoresponsive Polymersomes as Smart Triggerable Nanocarriers, in Soft Matter, 7(19), 9167-9176.
Can polymeric vesicles that confine enzymatic reactions act as simplified organelles?
Tanner Pascal, Egli Stefan, Balasubramanian Vimalkumar, Onaca Ozana, Palivan Cornelia G, Meier Wolfgang (2011), Can polymeric vesicles that confine enzymatic reactions act as simplified organelles?, in FEBS letters, 585(11), 1699-706.
Enzymatic cascade reactions inside polymeric nanocontainers: a means to combat oxidative stress.
Tanner Pascal, Onaca Ozana, Balasubramanian Vimalkumar, Meier Wolfgang, Palivan Cornelia G (2011), Enzymatic cascade reactions inside polymeric nanocontainers: a means to combat oxidative stress., in Chemistry (Weinheim an der Bergstrasse, Germany), 17(16), 4552-60.
Biocompatible functionalization of polymersome surfaces: a new approach to surface immobilization and cell targeting using polymersomes.
Egli Stefan, Nussbaumer Martin G, Balasubramanian Vimalkumar, Chami Mohamed, Bruns Nico, Palivan Cornelia, Meier Wolfgang (2011), Biocompatible functionalization of polymersome surfaces: a new approach to surface immobilization and cell targeting using polymersomes., in Journal of the American Chemical Society, 133(12), 4476-83.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Swiss Soft Days 8 08.06.2012 Geneva
Department conferences 02.04.2012 Osaka University
243rd ACS National Meeting 25.03.2012 San Diego USA
Makromolekulares Kolloquium 22.02.2012 Freiburg Germany
Workshop on the Biomolecules and Nanostructures 04.09.2011 Bedlewo, Poland
36Th FEBS Congress 25.06.2011 Torino, Italy
NanoBio Europe 21.06.2011 Cork Irland


Self-organised

Title Date Place
Swiss Soft Days 6 08.06.2011 Basel

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Hannover Messe 23.04.2012 Germany


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Science Slam Basel University German-speaking Switzerland 27.04.2012
New media (web, blogs, podcasts, news feeds etc.) UniNews Basel University news German-speaking Switzerland 23.04.2012

Awards

Title Year
2011 SCNAT/SCS Chemistry Travel Award 2011

Associated projects

Number Title Start Funding scheme
115956 Structure-activity relationships in Cu/Zn superoxide dismutase (SOD) and SOD-mimics before and after encapsulation in polymeric nanocontainers 01.04.2007 Project funding
140302 PROTEIN-POLYMER SUPRAMOLECULAR ASSEMBLIES IN THE DESIGN OF ANTIOXIDANT NANOREACTORS AND PROCESSORS 01.06.2012 Project funding
129968 STRUCTURE-ACTIVITY ANALYSIS OF SOD-MIMICS AND THEIR ENCAPSULATION IN NANOREACTORS 01.04.2010 Project funding
139133 Structure, dynamics and interactions of paramagnetic centers characterised by Electrn Paramagnetic Resonance 01.12.2011 R'EQUIP

Abstract

SUMMARYNanoreactors based on encapsulation of active compounds in polymeric carriers where they are able to act in situ have recently been developed as a new alternative to the conventional systems in use in various domains, such as catalysis or therapeutics. Amphiphilic block copolymers that auto-assemble in dilute solutions and form various architectures, as for example vesicles, represent efficient systems to design new nanoreactors, in combination with reactive molecules acting inside. Similar to liposomes from the point of view of molecule encapsulation, polymer nanovesicles are by far more stable and offer a better control of their properties, making them the preferred option for technological applications.Cu/Zn Superoxide dismutase (Cu/Zn-SOD) is known to act as an antioxidant enzyme by lowering the steady-state concentration of the superoxide radical anion (O2¯), which is responsible for oxidative stress in cells and has been implicated in the pathogenesis of many cardiovascular and pulmonary diseases. However, as Cu/Zn-SOD is quickly eliminated from the bloodstream, it provides rather modest protection, if any, when administered. Chemically and genetically modified Cu/Zn-SODs, coupled to polyethylene glycol (PEG) and encapsulated in liposomes, have been proposed as ways of improving the bioavailability of the protein, but none of them was able to enhance it significantly. The present study aims to design and test antioxidant nanoreactors based on the encapsulation of Cu/Zn-SOD (single-enzyme nanoreactor), or a tandem of SOD and a second enzyme (two-enzyme nanoreactor) for an efficient detoxification of superoxide radicals. In addition, we will combine inorganic, bioorganic, physical chemistry and EPR spectroscopic techniques in order to obtain a better understanding of the link between the structure and the role of the metal binding region of Cu/Zn-SOD before and after its confinement in nanocontainer cavities. As the catalytic site of the enzyme is the metal centre, detailed information about it when the enzyme is interacting with the polymer system, or is involved in a cascade reaction together with a second enzyme, can serve to gain insight into the relationship between the structure and catalytic activity, which is not yet fully understood. First, we will develop an antioxidant nanoreactor by encapsulating Cu/Zn-SOD in amphiphilic copolymer nanovesicles whose membrane is oxygen permeable. By changing the copolymer molecular properties, such as nature or length of the polymer blocks and hydrophobic-hydrophilic ratio, various constraints will be imposed on the protein in order to see if its active site is affected by its location inside vesicles, and to improve the effectiveness of the nanoreactor. Second, Cu/Zn-SOD will be co-encapsulated in polymeric nanocontainers together with an additional enzyme acting in a cascade reaction to allow a complete detoxification of superoxide radicals, with water as the final product. The polymer nanocontainers are a novel and more stable alternative to the liposome carriers, while preserving all the advantages of lipidic systems, such as lack of immunogenicity. The membrane of our triblock copolymer nanovesicles plays a double role, both to shield the sensitive protein and to selectively let superoxide and dioxygen penetrate to its inner space. In addition, the versatility of the chemistry of these polymeric carriers enables the control of several parameters, such as membrane permeability and vesicle size, in order to model various interactions in this hybrid system, and to improve its antioxidant function. Preliminary results have shown that the concept we introduce of a single-enzyme antioxidant nanoreactor is efficient, as the nanovesicles successfully encapsulated SOD during their self-assembling process, and the protein remained active inside. Our aim is to enhance its effectiveness for further biological applications associated with oxidative stress, and to improve in a quantified way the basic molecular understanding of the role of the metal coordination in Cu/Zn-SOD antioxidant function in various environmental conditions. The design of a complete antioxidant nanoreactor based on co-encapsulation of enzymes acting in tandem represents a new direction for developing drug delivery applications which avoids the disadvantages of conventional drug release systems.
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