Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors

Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability...

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Main Authors: Nuria Arias-Ramos, Luis Exequiel Ibarra, María Serrano-Torres, Balbino Yagüe, Matías Daniel Caverzán, Carlos Alberto Chesta, Rodrigo Emiliano Palacios, Pilar López-Larrubia
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/13/8/1258
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author Nuria Arias-Ramos
Luis Exequiel Ibarra
María Serrano-Torres
Balbino Yagüe
Matías Daniel Caverzán
Carlos Alberto Chesta
Rodrigo Emiliano Palacios
Pilar López-Larrubia
author_facet Nuria Arias-Ramos
Luis Exequiel Ibarra
María Serrano-Torres
Balbino Yagüe
Matías Daniel Caverzán
Carlos Alberto Chesta
Rodrigo Emiliano Palacios
Pilar López-Larrubia
author_sort Nuria Arias-Ramos
collection DOAJ
description Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low cytotoxicity, easy functionalization, and the ability to modify CPN photochemical properties by the incorporation of dopants, convert them into excellent theranostic agents with multifunctionality for imaging and treatment. In this work, CPNs were designed and synthesized by incorporating a metal oxide magnetic core (Fe<sub>3</sub>O<sub>4</sub> and NiFe<sub>2</sub>O<sub>4</sub> nanoparticles, 5 nm) into their matrix during the nanoprecipitation method. This modification allowed the in vivo monitoring of nanoparticles in animal models using magnetic resonance imaging (MRI) and intravital fluorescence, techniques widely used for intracranial tumors evaluation. The modified CPNs were assessed in vivo in glioblastoma (GBM) bearing mice, both heterotopic and orthotopic developed models. Biodistribution studies were performed with MRI acquisitions and fluorescence images up to 24 h after the i.v. nanoparticles administration. The resulting IONP-doped CPNs were biocompatible in GBM tumor cells in vitro with an excellent cell incorporation depending on nanoparticle concentration exposure. IONP-doped CPNs were detected in tumor and excretory organs of the heterotopic GBM model after i.v. and i.t. injection. However, in the orthotopic GBM model, the size of the nanoparticles is probably hindering a higher effect on intratumorally T2-weighted images (T<sub>2</sub>WI) signals and T<sub>2</sub> values. The photodynamic therapy (PDT)—cytotoxicity of CPNs was not either affected by the IONPs incorporation into the nanoparticles.
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spelling doaj.art-348571f5d5b241ab83fdca4ac0f81c582023-11-22T09:15:06ZengMDPI AGPharmaceutics1999-49232021-08-01138125810.3390/pharmaceutics13081258Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain TumorsNuria Arias-Ramos0Luis Exequiel Ibarra1María Serrano-Torres2Balbino Yagüe3Matías Daniel Caverzán4Carlos Alberto Chesta5Rodrigo Emiliano Palacios6Pilar López-Larrubia7Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, SpainInstituto de Biotecnología Ambiental y Salud (INBIAS), Universidad Nacional de Río Cuarto (UNRC) y CONICET, Córdoba X5800BIA, ArgentinaInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, SpainDepartamento de Biología Molecular, Facultad de Ciencias Exactas, Fisicoquímicas y Naturales, Universidad Nacional de Río Cuarto (UNRC), Córdoba X5800BIA, ArgentinaInstituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Universidad Nacional de Río Cuarto y CONICET, Córdoba X5800BIA, ArgentinaInstituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Universidad Nacional de Río Cuarto y CONICET, Córdoba X5800BIA, ArgentinaInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, SpainConjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low cytotoxicity, easy functionalization, and the ability to modify CPN photochemical properties by the incorporation of dopants, convert them into excellent theranostic agents with multifunctionality for imaging and treatment. In this work, CPNs were designed and synthesized by incorporating a metal oxide magnetic core (Fe<sub>3</sub>O<sub>4</sub> and NiFe<sub>2</sub>O<sub>4</sub> nanoparticles, 5 nm) into their matrix during the nanoprecipitation method. This modification allowed the in vivo monitoring of nanoparticles in animal models using magnetic resonance imaging (MRI) and intravital fluorescence, techniques widely used for intracranial tumors evaluation. The modified CPNs were assessed in vivo in glioblastoma (GBM) bearing mice, both heterotopic and orthotopic developed models. Biodistribution studies were performed with MRI acquisitions and fluorescence images up to 24 h after the i.v. nanoparticles administration. The resulting IONP-doped CPNs were biocompatible in GBM tumor cells in vitro with an excellent cell incorporation depending on nanoparticle concentration exposure. IONP-doped CPNs were detected in tumor and excretory organs of the heterotopic GBM model after i.v. and i.t. injection. However, in the orthotopic GBM model, the size of the nanoparticles is probably hindering a higher effect on intratumorally T2-weighted images (T<sub>2</sub>WI) signals and T<sub>2</sub> values. The photodynamic therapy (PDT)—cytotoxicity of CPNs was not either affected by the IONPs incorporation into the nanoparticles.https://www.mdpi.com/1999-4923/13/8/1258theranosticconjugated polymeriron oxide nanoparticlesglioblastomapreclinical trialsnanoparticles
spellingShingle Nuria Arias-Ramos
Luis Exequiel Ibarra
María Serrano-Torres
Balbino Yagüe
Matías Daniel Caverzán
Carlos Alberto Chesta
Rodrigo Emiliano Palacios
Pilar López-Larrubia
Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors
Pharmaceutics
theranostic
conjugated polymer
iron oxide nanoparticles
glioblastoma
preclinical trials
nanoparticles
title Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors
title_full Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors
title_fullStr Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors
title_full_unstemmed Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors
title_short Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors
title_sort iron oxide incorporated conjugated polymer nanoparticles for simultaneous use in magnetic resonance and fluorescent imaging of brain tumors
topic theranostic
conjugated polymer
iron oxide nanoparticles
glioblastoma
preclinical trials
nanoparticles
url https://www.mdpi.com/1999-4923/13/8/1258
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