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dc.contributor.authorPandya, Abhilash D.
dc.contributor.authorJäger, Eliézer
dc.contributor.authorFam, Shahla Bagheri
dc.contributor.authorHöcherl, Anita
dc.contributor.authorJäger, Alessandro
dc.contributor.authorSincari, Vladimir
dc.contributor.authorNyström, Bo
dc.contributor.authorŠtěpánek, Petr
dc.contributor.authorSkotland, Tore
dc.contributor.authorSandvig, Kirsten
dc.contributor.authorHrubý, Martin
dc.contributor.authorMælandsmo, Gunhild M.
dc.date.accessioned2019-10-15T08:42:01Z
dc.date.available2019-10-15T08:42:01Z
dc.date.issued2019-08-06
dc.description.abstract<i>Background</i>: Reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, trigger biodegradation of polymer-based nanoparticles (NPs) bearing pinacol-type boronic ester groups. These NPs may selectively release their cargo, in this case paclitaxel (PTX), at the high levels of ROS present in the intracellular environment of inflamed tissues and most tumors.<p> <p><i>Purpose</i>: The main objective was to determine anti-tumor efficacy of PTX-loaded ROS-sensitive NPs and to examine whether macrophage infiltration had any impact on treatment efficacy.<p> <p><i>Methods</i>: NPs were synthesized and their characteristics in the presence of H<sub>2</sub>O<sub>2</sub> were demonstrated. Both confocal microscopy as well as flow cytometry approaches were used to determine degradation of ROS-sensitive NPs. HeLa cells were cultured in vitro and used to establish tumor xenografts in nude mice. In vivo experiments were performed to understand toxicity, biodistribution and anti-tumor efficacy of the NPs. Moreover, we performed immunohistochemistry on tumor sections to study infiltration of M1 and M2 subsets of macrophages.<p> <p><i>Results</i>: We demonstrated that PTX delivered in NPs containing a ROS-sensitive polymer exhibits a better anti-tumor efficacy than PTX in NPs containing ROS-non-sensitive polymer, free PTX or Abraxane® (nab-PTX). The biodistribution revealed that ROS-sensitive NPs exhibit retention in liver, spleen and lungs, suggesting a potential to target cancer metastasizing to these organs. Finally, we demonstrated a correlation between infiltrated macrophage subsets and treatment efficacy, possibly contributing to the efficient anti-tumor effects.<p> <p><i>Conclusion</i>: Treatment with ROS-sensitive NPs containing PTX gave an improved therapeutic effect in HeLa xenografts than their counterpart, free PTX or nab-PTX. Our data revealed a correlation between macrophage infiltration and efficiency of the different antitumor treatments, as the most effective NPs resulted in the highest infiltration of the anti-tumorigenic M1 macrophages.en_US
dc.description.sponsorshipCzech Science Foundation Norwegian Grants Ministry of Education, Youth and Sportsen_US
dc.descriptionSource at <a href=https://doi.org/10.2147/IJN.S208938>https://doi.org/10.2147/IJN.S208938. </a>en_US
dc.identifier.citationPandya, A.D., Jäger, E., Fam, S.B., Höcherl, A., Jäger, A., Sincari, V. ... Mælandsmo, G.M. (2019). Paclitaxel-loaded biodegradable ROS-sensitive nanoparticles for cancer therapy. <i>International Journal of Nanomedicine, 14</i>, 6269-6285. https://doi.org/10.2147/IJN.S208938en_US
dc.identifier.cristinIDFRIDAID 1734519
dc.identifier.doi10.2147/IJN.S208938
dc.identifier.issn1176-9114
dc.identifier.issn1178-2013
dc.identifier.urihttps://hdl.handle.net/10037/16401
dc.language.isoengen_US
dc.publisherAmerican Society for Nanomedicineen_US
dc.relation.journalInternational Journal of Nanomedicine
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/NANO2021/228200/Norway/Biodegradable Nanoparticles in Cancer Diagnosis and Therapy//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.subjectreactive oxygen speciesen_US
dc.subjectROS-sensitive nanoparticlesen_US
dc.subjectpaclitaxelen_US
dc.subjecttreatment efficacyen_US
dc.subjectmacrophage infiltrationen_US
dc.titlePaclitaxel-loaded biodegradable ROS-sensitive nanoparticles for cancer therapyen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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