Bifunctional magnetopolymersomes of iron oxide nanoparticles and carboxymethylcellulose conjugated with doxorubicin for hyperthermo-chemotherapy of brain cancer cells

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dc.creatorSandhra Maria de Carvalho
dc.creatorAlice Gameiro Leonel
dc.creatorAlexandra Ancelmo Piscitelli Mansur
dc.creatorIsadora Cota Carvalho
dc.creatorKlaus Wilhelm Heinrich Krambrock
dc.creatorHerman Sander Mansur
dc.date.accessioned2022-12-16T16:52:32Z
dc.date.accessioned2025-09-09T01:28:50Z
dc.date.available2022-12-16T16:52:32Z
dc.date.issued2019
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipFINEP - Financiadora de Estudos e Projetos, Financiadora de Estudos e Projetos
dc.identifier.doihttps://doi.org/10.1039/c8bm01528g
dc.identifier.issn20474849
dc.identifier.urihttps://hdl.handle.net/1843/48155
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofBiomaterials Science
dc.rightsAcesso Restrito
dc.subjectAgentes antineoplásicos
dc.subjectTransporte biológico
dc.subjectNanopartículas
dc.subjectÓxido de ferro
dc.subject.otherAntineoplastic agents
dc.subject.otherBiological transport
dc.subject.otherNanoparticles
dc.subject.otherFerrosoferric oxide
dc.titleBifunctional magnetopolymersomes of iron oxide nanoparticles and carboxymethylcellulose conjugated with doxorubicin for hyperthermo-chemotherapy of brain cancer cells
dc.typeArtigo de periódico
local.citation.epage2122
local.citation.issue5
local.citation.spage2102
local.citation.volume7
local.description.resumoGlioblastoma is the most aggressive primary brain cancer, which has no cure yet. Emerging nanotheranostic alternatives such as magnetic iron oxide nanoparticles (MIONs) have great potential as multimodal cancer therapy mediators. They can act as nanocarriers of anticancer drugs and generate localized heat when exposed to an alternating magnetic field (AMF), resulting in combined effects of chemotherapy and magnetic hyperthermia therapy. Thus, we designed and synthesized novel MIONs directly through a co-precipitation method by a single step one-pot aqueous green process using carboxymethylcellulose (CMC) as a multifunctional, biocompatible and water-soluble biopolymer ligand (iron oxide nanoparticle-CMC, MION@CMC). They were bioconjugated via amide bonds with doxorubicin (DOX, an anticancer drug) forming nanohybrids (MION@CMC-DOX). The CMC, MION@CMC and MION@CMC-DOX nanoconjugates were comprehensively characterized by 1HNMR, FTIR, TEM/SAED/EDX, UV-visible, XRD, zeta potential (ZP) and DLS analyses. Moreover, cytotoxicity and cell killing activities of these nanoconjugates were assessed by in vitro biological assays. The nanoconjugates were incubated with glioma cells (U87), a magnetic hyperthermia (MHT) assay was performed for evaluating the activity against brain cancer cells and confocal laser scanning laser microscopy was used for bioimaging their cellular uptake pathways. The results showed that fairly monodisperse and water-soluble ultra-small iron oxide nanoparticles (Fe3O4) were synthesized (core size = 7 ± 2 nm) and stabilized by CMC producing negatively charged nanocolloids (-38 ± 3 mV, MION@CMC; hydrodynamic radius, HD = 38 ± 2 nm). The results confirmed the conjugation of MION@CMC with DOX by amide bonds, leading to the development of magnetopolymersome nanostructures (MION@CMC-DOX). The cell viability bioassays evidenced low toxicity of MION@CMC compared to the severe cytotoxicity of MION@CMC-DOX nanosystems mainly caused by the release of DOX. Under an alternating magnetic field, MION@CMC and MION@CMC-DOX systems demonstrated activity for killing U87 cancer cells due to the heat generated by hyperthermia. In addition, the MION@CMC-DOX bioconjugates showed significantly higher cell killing response when exposed to an AMF due to the combined chemotherapy effect of DOX release inside the cancer cells triggering apoptotic pathways.
local.identifier.orcidhttps://orcid.org/0000-0002-8798-4182
local.identifier.orcidhttps://orcid.org/0000-0003-1526-2508
local.identifier.orcidhttps://orcid.org/0000-0003-2929-3452
local.identifier.orcidhttps://orcid.org/0000-0002-7562-0285
local.identifier.orcidhttps://orcid.org/0000-0002-3032-495X
local.publisher.countryBrasil
local.publisher.departmentENG - DEPARTAMENTO DE ENGENHARIA METALÚRGICA
local.publisher.departmentICX - DEPARTAMENTO DE FÍSICA
local.publisher.initialsUFMG
local.url.externahttps://pubs.rsc.org/en/content/articlelanding/2019/BM/C8BM01528G

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