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Polyelectrolyte-protein synergism: pH-responsive polyelectrolyte/insulin complexes as versatile carriers for targeted protein and drug delivery.
Murmiliuk, Anastasiia; Iwase, Hiroki; Kang, Jia-Jhen; Mohanakumar, Shilpa; Appavou, Marie-Sousai; Wood, Kathleen; Almásy, László; Len, Adél; Schwärzer, Kuno; Allgaier, Jürgen; Dulle, Martin; Gensch, Thomas; Förster, Beate; Ito, Kanae; Nakagawa, Hiroshi; Wiegand, Simone; Förster, Stephan; Radulescu, Aurel.
Afiliación
  • Murmiliuk A; Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jülich GmbH, Lichtenbergstraße 1, 85747 Garching, Germany. Electronic address: anastasiia.murmiliuk@gmail.com.
  • Iwase H; Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS), Tokai, Ibaraki 319-1106, Japan.
  • Kang JJ; Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jülich GmbH, Lichtenbergstraße 1, 85747 Garching, Germany.
  • Mohanakumar S; Physics of Complex Fluids, University of Twente, 7522 NB Enschede, The Netherlands.
  • Appavou MS; Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jülich GmbH, Lichtenbergstraße 1, 85747 Garching, Germany.
  • Wood K; Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organization, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
  • Almásy L; Neutron Spectroscopy Department, HUN-REN Centre for Energy Research, Konkoly-Thege str. 29-33, 1121 Budapest, Hungary.
  • Len A; Neutron Spectroscopy Department, HUN-REN Centre for Energy Research, Konkoly-Thege str. 29-33, 1121 Budapest, Hungary; University of Pécs, Faculty of Engineering and Information Technology, Boszorkány str 2., 7624 Pécs, Hungary.
  • Schwärzer K; Jülich Centre for Neutron Science (JCNS-1/IBI-8), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
  • Allgaier J; Jülich Centre for Neutron Science (JCNS-1/IBI-8), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
  • Dulle M; Jülich Centre for Neutron Science (JCNS-1/IBI-8), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
  • Gensch T; Institute of Biological Information Processing, IBI-1 (Molecular and Cellular Physiology), Forschungszentrum Jülich, 52425 Jülich, Germany.
  • Förster B; Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons, Physics of Nanoscale Systems (ER-C-1), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
  • Ito K; Industrial Application Division, Spring-8, Japan Synchrotron Radiation Research Institute (JASRI), 1-1-1 Kouto, Sayo, Hyogo 679-5198, Japan.
  • Nakagawa H; Materials Sciences Research Center, Japan Atomic Energy Agency, Tokai, Ibaraki, Japan.
  • Wiegand S; IBI-4-Biomacromolecular Systems and Processes, Forschungszentrum Jülich GmbH, D-52428 Jülich, Germany; Chemistry Department - Physical Chemistry, University Cologne, D-50939 Cologne, Germany.
  • Förster S; Jülich Centre for Neutron Science (JCNS-1/IBI-8), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
  • Radulescu A; Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jülich GmbH, Lichtenbergstraße 1, 85747 Garching, Germany.
J Colloid Interface Sci ; 665: 801-813, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38555748
ABSTRACT
The co-assembly of polyelectrolytes (PE) with proteins offers a promising approach for designing complex structures with customizable morphologies, charge distribution, and stability for targeted cargo delivery. However, the complexity of protein structure limits our ability to predict the properties of the formed nanoparticles, and our goal is to identify the key triggers of the morphological transition in protein/PE complexes and evaluate their ability to encapsulate multivalent ionic drugs. A positively charged PE can assemble with a protein at pH above isoelectric point due to the electrostatic attraction and disassemble at pH below isoelectric point due to the repulsion. The additional hydrophilic block of the polymer should stabilize the particles in solution and enable them to encapsulate a negatively charged drug in the presence of PE excess. We demonstrated that diblock copolymers, poly(ethylene oxide)-block-poly(N,N-dimethylaminoethyl methacrylate) and poly(ethylene oxide)-block-poly(N,N,N-trimethylammonioethyl methacrylate), consisting of a polycation block and a neutral hydrophilic block, reversibly co-assemble with insulin in pH range between 5 and 8. Using small-angle neutron and X-ray scattering (SANS, SAXS), we showed that insulin arrangement within formed particles is controlled by intermolecular electrostatic forces between protein molecules, and can be tuned by varying ionic strength. For the first time, we observed by fluorescence that formed protein/PE complexes with excess of positive charges exhibited potential for encapsulating and controlled release of negatively charged bivalent drugs, protoporphyrin-IX and zinc(II) protoporphyrin-IX, enabling the development of nanocarriers for combination therapies with adjustable charge, stability, internal structure, and size.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protoporfirinas / Insulina Idioma: En Revista: J Colloid Interface Sci Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protoporfirinas / Insulina Idioma: En Revista: J Colloid Interface Sci Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos