Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

Harald Unterweger,1 Daniel Subatzus,1 Rainer Tietze,1 Christina Janko,1 Marina Poettler,1 Alfons Stiegelschmitt,2 Matthias Schuster,3 Caroline Maake,4 Aldo R Boccaccini,5 Christoph Alexiou11ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stift...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Unterweger H, Subatzus D, Tietze R, Janko C, Poettler M, Stiegelschmitt A, Schuster M, Maake C, Boccaccini AR, Alexiou C
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://doaj.org/article/d78b41ed170c47c0a43a78dfff9b8d9e
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:d78b41ed170c47c0a43a78dfff9b8d9e
record_format dspace
spelling oai:doaj.org-article:d78b41ed170c47c0a43a78dfff9b8d9e2021-12-02T05:09:49ZHypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy1178-2013https://doaj.org/article/d78b41ed170c47c0a43a78dfff9b8d9e2015-11-01T00:00:00Zhttps://www.dovepress.com/hypericin-bearing-magnetic-iron-oxide-nanoparticles-for-selective-drug-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Harald Unterweger,1 Daniel Subatzus,1 Rainer Tietze,1 Christina Janko,1 Marina Poettler,1 Alfons Stiegelschmitt,2 Matthias Schuster,3 Caroline Maake,4 Aldo R Boccaccini,5 Christoph Alexiou11ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen; 2Institute of Glass and Ceramics, Department of Materials Science and Engineering, University Erlangen-Nuremberg, 3Materials for Electronics and Energy Technology, Department of Materials Science and Engineering, University Erlangen-Nürnberg, Erlangen, Germany; 4Institute of Anatomy, University of Zurich, Winterthurerstr, Zurich, Switzerland; 5Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany Abstract: Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55–85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5–5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ζ potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs’ targeting abilities with hypericin’s phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer. Keywords: magnetic drug targeting, photodynamic therapy, SPION, hypericinUnterweger HSubatzus DTietze RJanko CPoettler MStiegelschmitt ASchuster MMaake CBoccaccini ARAlexiou CDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6985-6996 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Unterweger H
Subatzus D
Tietze R
Janko C
Poettler M
Stiegelschmitt A
Schuster M
Maake C
Boccaccini AR
Alexiou C
Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy
description Harald Unterweger,1 Daniel Subatzus,1 Rainer Tietze,1 Christina Janko,1 Marina Poettler,1 Alfons Stiegelschmitt,2 Matthias Schuster,3 Caroline Maake,4 Aldo R Boccaccini,5 Christoph Alexiou11ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen; 2Institute of Glass and Ceramics, Department of Materials Science and Engineering, University Erlangen-Nuremberg, 3Materials for Electronics and Energy Technology, Department of Materials Science and Engineering, University Erlangen-Nürnberg, Erlangen, Germany; 4Institute of Anatomy, University of Zurich, Winterthurerstr, Zurich, Switzerland; 5Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany Abstract: Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55–85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5–5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ζ potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs’ targeting abilities with hypericin’s phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer. Keywords: magnetic drug targeting, photodynamic therapy, SPION, hypericin
format article
author Unterweger H
Subatzus D
Tietze R
Janko C
Poettler M
Stiegelschmitt A
Schuster M
Maake C
Boccaccini AR
Alexiou C
author_facet Unterweger H
Subatzus D
Tietze R
Janko C
Poettler M
Stiegelschmitt A
Schuster M
Maake C
Boccaccini AR
Alexiou C
author_sort Unterweger H
title Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy
title_short Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy
title_full Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy
title_fullStr Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy
title_full_unstemmed Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy
title_sort hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/d78b41ed170c47c0a43a78dfff9b8d9e
work_keys_str_mv AT unterwegerh hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT subatzusd hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT tietzer hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT jankoc hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT poettlerm hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT stiegelschmitta hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT schusterm hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT maakec hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT boccacciniar hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
AT alexiouc hypericinbearingmagneticironoxidenanoparticlesforselectivedrugdeliveryinphotodynamictherapy
_version_ 1718400563944620032