Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1021/acs.molpharmaceut.9b01094 http://hdl.handle.net/11449/198599 |
Resumo: | Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results. |
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Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Studyiron oxide-based nanoparticlesmagnetic hyperthermiamembrane-coated nanoparticlesnear-infrared dyepharmacokinetic modelphotothermal therapytumor delivery efficiencyDelivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.Physics Institute Federal University of GoiásBiomagnetism Lab Physics and Biophysics Department São Paulo State UniversityLaboratory of Pharmaceutical Nanotechnology and Drug Delivery Systems School of Pharmacy Federal University of GoiásBiological Sciences Institute Federal University of GoiásBiomagnetism Lab Physics and Biophysics Department São Paulo State UniversityUniversidade Federal de Goiás (UFG)Universidade Estadual Paulista (Unesp)Sousa-Junior, Ailton A.Mendanha, Sebastião A.Carrião, Marcus S.Capistrano, GustavoPróspero, André G. [UNESP]Soares, Guilherme A. [UNESP]Cintra, Emílio R.Santos, Sônia F.O.Zufelato, NicholasAlonso, AntônioLima, Eliana M.Miranda, José Ricardo A. [UNESP]Silveira-Lacerda, Elisângela De P.Cardoso, Cléver G.Bakuzis, Andris F.2020-12-12T01:17:17Z2020-12-12T01:17:17Z2020-03-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article837-851http://dx.doi.org/10.1021/acs.molpharmaceut.9b01094Molecular Pharmaceutics, v. 17, n. 3, p. 837-851, 2020.1543-83921543-8384http://hdl.handle.net/11449/19859910.1021/acs.molpharmaceut.9b010942-s2.0-85081072742Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMolecular Pharmaceuticsinfo:eu-repo/semantics/openAccess2021-10-22T17:19:55Zoai:repositorio.unesp.br:11449/198599Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-22T17:19:55Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study |
title |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study |
spellingShingle |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study Sousa-Junior, Ailton A. iron oxide-based nanoparticles magnetic hyperthermia membrane-coated nanoparticles near-infrared dye pharmacokinetic model photothermal therapy tumor delivery efficiency |
title_short |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study |
title_full |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study |
title_fullStr |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study |
title_full_unstemmed |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study |
title_sort |
Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study |
author |
Sousa-Junior, Ailton A. |
author_facet |
Sousa-Junior, Ailton A. Mendanha, Sebastião A. Carrião, Marcus S. Capistrano, Gustavo Próspero, André G. [UNESP] Soares, Guilherme A. [UNESP] Cintra, Emílio R. Santos, Sônia F.O. Zufelato, Nicholas Alonso, Antônio Lima, Eliana M. Miranda, José Ricardo A. [UNESP] Silveira-Lacerda, Elisângela De P. Cardoso, Cléver G. Bakuzis, Andris F. |
author_role |
author |
author2 |
Mendanha, Sebastião A. Carrião, Marcus S. Capistrano, Gustavo Próspero, André G. [UNESP] Soares, Guilherme A. [UNESP] Cintra, Emílio R. Santos, Sônia F.O. Zufelato, Nicholas Alonso, Antônio Lima, Eliana M. Miranda, José Ricardo A. [UNESP] Silveira-Lacerda, Elisângela De P. Cardoso, Cléver G. Bakuzis, Andris F. |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Goiás (UFG) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Sousa-Junior, Ailton A. Mendanha, Sebastião A. Carrião, Marcus S. Capistrano, Gustavo Próspero, André G. [UNESP] Soares, Guilherme A. [UNESP] Cintra, Emílio R. Santos, Sônia F.O. Zufelato, Nicholas Alonso, Antônio Lima, Eliana M. Miranda, José Ricardo A. [UNESP] Silveira-Lacerda, Elisângela De P. Cardoso, Cléver G. Bakuzis, Andris F. |
dc.subject.por.fl_str_mv |
iron oxide-based nanoparticles magnetic hyperthermia membrane-coated nanoparticles near-infrared dye pharmacokinetic model photothermal therapy tumor delivery efficiency |
topic |
iron oxide-based nanoparticles magnetic hyperthermia membrane-coated nanoparticles near-infrared dye pharmacokinetic model photothermal therapy tumor delivery efficiency |
description |
Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T01:17:17Z 2020-12-12T01:17:17Z 2020-03-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1021/acs.molpharmaceut.9b01094 Molecular Pharmaceutics, v. 17, n. 3, p. 837-851, 2020. 1543-8392 1543-8384 http://hdl.handle.net/11449/198599 10.1021/acs.molpharmaceut.9b01094 2-s2.0-85081072742 |
url |
http://dx.doi.org/10.1021/acs.molpharmaceut.9b01094 http://hdl.handle.net/11449/198599 |
identifier_str_mv |
Molecular Pharmaceutics, v. 17, n. 3, p. 837-851, 2020. 1543-8392 1543-8384 10.1021/acs.molpharmaceut.9b01094 2-s2.0-85081072742 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecular Pharmaceutics |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
837-851 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965534842781696 |