Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles

Jessica Perez, Javier Cifuentes, Monica Cuellar, Alejandra Suarez-Arnedo, Juan C Cruz, Carolina Muñoz-Camargo GINIB Research Group, Department of Biomedical Engineering, Universidad de los Andes, Bogotá, ColombiaCorrespondence: Carolina Muñoz-Camargo; Juan C Cruz Tel...

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Autores principales:	Perez J, Cifuentes J, Cuellar M, Suarez-Arnedo A, Cruz JC, Muñoz-Camargo C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Buforin-II conjugates drug delivery translocation Cell-penetrating peptides nanomaterials Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/baa862bac4584d17bedf6b496fe1f5e7
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spelling	oai:doaj.org-article:baa862bac4584d17bedf6b496fe1f5e72021-12-02T03:48:44ZCell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles1178-2013https://doaj.org/article/baa862bac4584d17bedf6b496fe1f5e72019-10-01T00:00:00Zhttps://www.dovepress.com/cell-penetrating-and-antibacterial-buf-ii-nanobioconjugates-enhanced-p-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jessica Perez, Javier Cifuentes, Monica Cuellar, Alejandra Suarez-Arnedo, Juan C Cruz, Carolina Muñoz-Camargo GINIB Research Group, Department of Biomedical Engineering, Universidad de los Andes, Bogotá, ColombiaCorrespondence: Carolina Muñoz-Camargo; Juan C Cruz Tel +57-1 3394949 Ext. 1789, 1853Email c.munoz2016@uniandes.edu.co; jc.cruz@uniandes.edu.coIntroduction: Controlled delivery of therapeutic molecules in a localized manner has become an area of interest due to its potential to reduce drug exposure to healthy tissues and consequently to minimize undesirable side effects. We have recently introduced novel cell-penetrating vehicles by immobilizing the antimicrobial peptide Buforin II (BUF-II) on magnetite nanoparticles (MPNPs). Despite the potent translocating abilities of such nanobioconjugates, they failed to preserve the antimicrobial activity of native BUF-II. In this work, we explored immobilization on MNPs with the aid of polymer surface spacers, which has been considered as an attractive alternative for the highly efficient conjugation of various biomolecules.Methods: Here, we immobilized BUF-II on polyetheramine-modified magnetite nanoparticles to preserve its structural integrity. As a result, for the obtained nanobioconjugates the lost antimicrobial activity against gram-positive and gram-negative bacteria was only 50% with respect to the native BUF-II. The nanobioconjugates were also characterized via FTIR, DLS, TEM, and TGA. Delivery on THP-1, HaCaT, HFF, and Escherichia coli cells was conducted to confirm capability for cell membrane translocation.Results: Colocalization with Lysotracker showed an endosomal escape efficiency of about 73∓12% in THP-1 cells. Avoidance of endocytic pathways of internalization was qualitatively confirmed by a delivery assay at low temperature. Nuclear penetration of the nanobioconjugates was corroborated via confocal microscopy and showed high biocompatibility as demonstrated by hemolysis levels below 5% and acute cytotoxicity of around 15%.Conclusion: The obtained nanobioconjugates were capable of translocating the cell membrane and nuclei of different normal and cancerous cell lines without significantly decreasing viability. This makes the vehicle addressable for a number of applications ranging from antimicrobial topical treatments to the delivery of nucleotides and therapeutic molecules with difficulties to bypass cell membranes.Keywords: Buforin-II conjugates, drug delivery, translocation, cell-penetrating peptides, nanomaterialsPerez JCifuentes JCuellar MSuarez-Arnedo ACruz JCMuñoz-Camargo CDove Medical PressarticleBuforin-II conjugatesdrug deliverytranslocationCell-penetrating peptidesnanomaterialsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8483-8497 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Buforin-II conjugates drug delivery translocation Cell-penetrating peptides nanomaterials Medicine (General) R5-920
spellingShingle	Buforin-II conjugates drug delivery translocation Cell-penetrating peptides nanomaterials Medicine (General) R5-920 Perez J Cifuentes J Cuellar M Suarez-Arnedo A Cruz JC Muñoz-Camargo C Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles
description	Jessica Perez, Javier Cifuentes, Monica Cuellar, Alejandra Suarez-Arnedo, Juan C Cruz, Carolina Muñoz-Camargo GINIB Research Group, Department of Biomedical Engineering, Universidad de los Andes, Bogotá, ColombiaCorrespondence: Carolina Muñoz-Camargo; Juan C Cruz Tel +57-1 3394949 Ext. 1789, 1853Email c.munoz2016@uniandes.edu.co; jc.cruz@uniandes.edu.coIntroduction: Controlled delivery of therapeutic molecules in a localized manner has become an area of interest due to its potential to reduce drug exposure to healthy tissues and consequently to minimize undesirable side effects. We have recently introduced novel cell-penetrating vehicles by immobilizing the antimicrobial peptide Buforin II (BUF-II) on magnetite nanoparticles (MPNPs). Despite the potent translocating abilities of such nanobioconjugates, they failed to preserve the antimicrobial activity of native BUF-II. In this work, we explored immobilization on MNPs with the aid of polymer surface spacers, which has been considered as an attractive alternative for the highly efficient conjugation of various biomolecules.Methods: Here, we immobilized BUF-II on polyetheramine-modified magnetite nanoparticles to preserve its structural integrity. As a result, for the obtained nanobioconjugates the lost antimicrobial activity against gram-positive and gram-negative bacteria was only 50% with respect to the native BUF-II. The nanobioconjugates were also characterized via FTIR, DLS, TEM, and TGA. Delivery on THP-1, HaCaT, HFF, and Escherichia coli cells was conducted to confirm capability for cell membrane translocation.Results: Colocalization with Lysotracker showed an endosomal escape efficiency of about 73∓12% in THP-1 cells. Avoidance of endocytic pathways of internalization was qualitatively confirmed by a delivery assay at low temperature. Nuclear penetration of the nanobioconjugates was corroborated via confocal microscopy and showed high biocompatibility as demonstrated by hemolysis levels below 5% and acute cytotoxicity of around 15%.Conclusion: The obtained nanobioconjugates were capable of translocating the cell membrane and nuclei of different normal and cancerous cell lines without significantly decreasing viability. This makes the vehicle addressable for a number of applications ranging from antimicrobial topical treatments to the delivery of nucleotides and therapeutic molecules with difficulties to bypass cell membranes.Keywords: Buforin-II conjugates, drug delivery, translocation, cell-penetrating peptides, nanomaterials
format	article
author	Perez J Cifuentes J Cuellar M Suarez-Arnedo A Cruz JC Muñoz-Camargo C
author_facet	Perez J Cifuentes J Cuellar M Suarez-Arnedo A Cruz JC Muñoz-Camargo C
author_sort	Perez J
title	Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles
title_short	Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles
title_full	Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles
title_fullStr	Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles
title_full_unstemmed	Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles
title_sort	cell-penetrating and antibacterial buf-ii nanobioconjugates: enhanced potency via immobilization on polyetheramine-modified magnetite nanoparticles
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/baa862bac4584d17bedf6b496fe1f5e7
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Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles

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