Bioengineering the spider silk sequence to modify its affinity for drugs

Kamil Kucharczyk,1,2 Marek Weiss,3 Katarzyna Jastrzebska,1,2 Magdalena Luczak,4,5 Arkadiusz Ptak,3 Maciej Kozak,6,7 Andrzej Mackiewicz,1,2 Hanna Dams-Kozlowska1,2 1Department of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland; 2Department of Diagnostics and Cancer Immun...

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Autores principales:	Kucharczyk K, Weiss M, Jastrzebska K, Luczak M, Ptak A, Kozak M, Mackiewicz A, Dams-Kozlowska H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	silk bioengineering spheres drug delivery chemotherapeutics cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e1acfe36b1934390b64855dfb2501a69
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spelling	oai:doaj.org-article:e1acfe36b1934390b64855dfb2501a692021-12-02T04:14:08ZBioengineering the spider silk sequence to modify its affinity for drugs1178-2013https://doaj.org/article/e1acfe36b1934390b64855dfb2501a692018-07-01T00:00:00Zhttps://www.dovepress.com/bioengineering-the-spider-silk-sequence-to-modify-its-affinity-for-dru-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kamil Kucharczyk,1,2 Marek Weiss,3 Katarzyna Jastrzebska,1,2 Magdalena Luczak,4,5 Arkadiusz Ptak,3 Maciej Kozak,6,7 Andrzej Mackiewicz,1,2 Hanna Dams-Kozlowska1,2 1Department of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland; 2Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland; 3Division of Computational Physics and Nanomechanics, Institute of Physics, Faculty of Technical Physics, Poznan University of Technology, Poznan, Poland; 4Department of Biomedical Proteomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland; 5Department of Organic Chemistry, Institute of Chemical Technology and Engineering, Poznan University of Technology, Poznan, Poland; 6Department of Macromolecular Physics, Adam Mickiewicz University, Poznan, Poland; 7Joint Laboratory for SAXS Studies, Adam Mickiewicz University, Poznan, Poland Background: Silk is a biocompatible and biodegradable material, able to self-assemble into different morphological structures. Silk structures may be used for many biomedical applications, including carriers for drug delivery. The authors designed a new bioengineered spider silk protein, EMS2, and examined its property as a carrier of chemotherapeutics.Materials and methods: To obtain EMS protein, the MS2 silk monomer (that was based on the MaSp2 spidroin of Nephila clavipes) was modified by the addition of a glutamic acid residue. Both bioengineered silks were produced in an Escherichia coli expression system and purified by thermal method. The silk spheres were produced by mixing with potassium phosphate buffer. The physical properties of the particles were characterized using scanning electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, and zeta potential measurements. The MTT assay was used to examine the cytotoxicity of spheres. The loading and release profiles of drugs were studied spectrophotometrically.Results: The bioengineered silk variant, EMS2, was constructed, produced, and purified. The EMS2 silk retained the self-assembly property and formed spheres. The spheres made of EMS2 and MS2 silks were not cytotoxic and had a similar secondary structure content but differed in morphology and zeta potential values; EMS2 particles were more negatively charged than MS2 particles. Independently of the loading method (pre- or post-loading), the loading of drugs into EMS2 spheres was more efficient than the loading into MS2 spheres. The advantageous loading efficiency and release rate made EMS2 spheres a good choice to deliver neutral etoposide (ETP). Despite the high loading efficiency of positively charged mitoxantrone (MTX) into EMS2 particles, the fast release rate made EMS2 unsuitable for the delivery of this drug. A faster release rate from EMS2 particles compared to MS2 particles was observed for positively charged doxorubicin (DOX).Conclusion: By modifying its sequence, silk affinity for drugs can be controlled. Keywords: silk, bioengineering, spheres, drug delivery, chemotherapeutics, cancer therapyKucharczyk KWeiss MJastrzebska KLuczak MPtak AKozak MMackiewicz ADams-Kozlowska HDove Medical Pressarticlesilkbioengineeringspheresdrug deliverychemotherapeuticscancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4247-4261 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	silk bioengineering spheres drug delivery chemotherapeutics cancer Medicine (General) R5-920
spellingShingle	silk bioengineering spheres drug delivery chemotherapeutics cancer Medicine (General) R5-920 Kucharczyk K Weiss M Jastrzebska K Luczak M Ptak A Kozak M Mackiewicz A Dams-Kozlowska H Bioengineering the spider silk sequence to modify its affinity for drugs
description	Kamil Kucharczyk,1,2 Marek Weiss,3 Katarzyna Jastrzebska,1,2 Magdalena Luczak,4,5 Arkadiusz Ptak,3 Maciej Kozak,6,7 Andrzej Mackiewicz,1,2 Hanna Dams-Kozlowska1,2 1Department of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland; 2Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland; 3Division of Computational Physics and Nanomechanics, Institute of Physics, Faculty of Technical Physics, Poznan University of Technology, Poznan, Poland; 4Department of Biomedical Proteomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland; 5Department of Organic Chemistry, Institute of Chemical Technology and Engineering, Poznan University of Technology, Poznan, Poland; 6Department of Macromolecular Physics, Adam Mickiewicz University, Poznan, Poland; 7Joint Laboratory for SAXS Studies, Adam Mickiewicz University, Poznan, Poland Background: Silk is a biocompatible and biodegradable material, able to self-assemble into different morphological structures. Silk structures may be used for many biomedical applications, including carriers for drug delivery. The authors designed a new bioengineered spider silk protein, EMS2, and examined its property as a carrier of chemotherapeutics.Materials and methods: To obtain EMS protein, the MS2 silk monomer (that was based on the MaSp2 spidroin of Nephila clavipes) was modified by the addition of a glutamic acid residue. Both bioengineered silks were produced in an Escherichia coli expression system and purified by thermal method. The silk spheres were produced by mixing with potassium phosphate buffer. The physical properties of the particles were characterized using scanning electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, and zeta potential measurements. The MTT assay was used to examine the cytotoxicity of spheres. The loading and release profiles of drugs were studied spectrophotometrically.Results: The bioengineered silk variant, EMS2, was constructed, produced, and purified. The EMS2 silk retained the self-assembly property and formed spheres. The spheres made of EMS2 and MS2 silks were not cytotoxic and had a similar secondary structure content but differed in morphology and zeta potential values; EMS2 particles were more negatively charged than MS2 particles. Independently of the loading method (pre- or post-loading), the loading of drugs into EMS2 spheres was more efficient than the loading into MS2 spheres. The advantageous loading efficiency and release rate made EMS2 spheres a good choice to deliver neutral etoposide (ETP). Despite the high loading efficiency of positively charged mitoxantrone (MTX) into EMS2 particles, the fast release rate made EMS2 unsuitable for the delivery of this drug. A faster release rate from EMS2 particles compared to MS2 particles was observed for positively charged doxorubicin (DOX).Conclusion: By modifying its sequence, silk affinity for drugs can be controlled. Keywords: silk, bioengineering, spheres, drug delivery, chemotherapeutics, cancer therapy
format	article
author	Kucharczyk K Weiss M Jastrzebska K Luczak M Ptak A Kozak M Mackiewicz A Dams-Kozlowska H
author_facet	Kucharczyk K Weiss M Jastrzebska K Luczak M Ptak A Kozak M Mackiewicz A Dams-Kozlowska H
author_sort	Kucharczyk K
title	Bioengineering the spider silk sequence to modify its affinity for drugs
title_short	Bioengineering the spider silk sequence to modify its affinity for drugs
title_full	Bioengineering the spider silk sequence to modify its affinity for drugs
title_fullStr	Bioengineering the spider silk sequence to modify its affinity for drugs
title_full_unstemmed	Bioengineering the spider silk sequence to modify its affinity for drugs
title_sort	bioengineering the spider silk sequence to modify its affinity for drugs
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/e1acfe36b1934390b64855dfb2501a69
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_version_	1718401401453805568

Bioengineering the spider silk sequence to modify its affinity for drugs

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