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Colocalized delivery of rapamycin and paclitaxel to tumors enhances synergistic targeting of the PI3K/Akt/mTOR pathway

dc.creatorCarlos Alberto González Delgado
dc.date2014
dc.date.accessioned2018-10-18T20:12:51Z
dc.date.available2018-10-18T20:12:51Z
dc.identifier.issn15250016
dc.identifier.doi10.1038/mt.2014.27
dc.identifier.urihttp://hdl.handle.net/11285/630309
dc.descriptionOngoing clinical trials target the aberrant PI3K/Akt/mammalian target of rapamycin (mTOR) pathway in breast cancer through administration of rapamycin, an allosteric mTOR inhibitor, in combination with paclitaxel. However, synergy may not be fully exploited clinically because of distinct pharmacokinetic parameters of drugs. This study explores the synergistic potential of site-specific, colocalized delivery of rapamycin and paclitaxel through nanoparticle incorporation. Nanoparticle drug loading was accurately controlled, and synergistic drug ratios established in vitro. Precise drug ratios were maintained in tumors 48 hours after nanoparticle administration to mice, at levels twofold greater than liver and spleen, yielding superior antitumor activity compared to controls. Simultaneous and preferential in vivo delivery of rapamycin and paclitaxel to tumors yielded mechanistic insights into synergy involving suppression of feedback loop Akt phosphorylation and its downstream targets. Findings demonstrate that a same time, same place, and specific amount approach to combination chemotherapy by means of nanoparticle delivery has the potential to successfully translate in vitro synergistic findings in vivo. Predictive in vitro models can be used to determine optimum drug ratios for antitumor efficacy, while nanoparticle delivery of combination chemotherapies in preclinical animal models may lead to enhanced understanding of mechanisms of synergy, ultimately opening several avenues for personalized therapy. © The American Society of Gene & Cell Therapy.
dc.languageeng
dc.publisherNature Publishing Group
dc.relationhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84903759913&doi=10.1038%2fmt.2014.27&partnerID=40&md5=8f19aaba3365f84d7c33f08916ec8eb8
dc.relationInvestigadores
dc.relationEstudiantes
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourceMolecular Therapy
dc.subjectmammalian target of rapamycin
dc.subjectnanoparticle
dc.subjectpaclitaxel
dc.subjectphosphatidylinositol 3 kinase
dc.subjectprotein kinase B
dc.subjectrapamycin
dc.subjectpaclitaxel
dc.subjectphosphatidylinositol 3 kinase
dc.subjectprotein kinase B
dc.subjectrapamycin
dc.subjecttarget of rapamycin kinase
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantineoplastic activity
dc.subjectbreast cancer
dc.subjectcancer inhibition
dc.subjectconference paper
dc.subjectcontrolled study
dc.subjectdrug delivery system
dc.subjectdrug potentiation
dc.subjectdrug tumor level
dc.subjectfemale
dc.subjectin vitro study
dc.subjectliver
dc.subjectmouse
dc.subjectnanoencapsulation
dc.subjectnanopharmaceutics
dc.subjectnonhuman
dc.subjectparticle size
dc.subjectprotein phosphorylation
dc.subjectprotein targeting
dc.subjectspleen
dc.subjectanimal
dc.subjectapoptosis
dc.subjectcell proliferation
dc.subjectdrug effects
dc.subjecthuman
dc.subjectMammary Neoplasms, Animal
dc.subjectMCF 7 cell line
dc.subjectmetabolism
dc.subjectnude mouse
dc.subjectsignal transduction
dc.subjecttumor cell line
dc.subjectAnimalia
dc.subjectMus
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectFemale
dc.subjectHumans
dc.subjectMammary Neoplasms, Animal
dc.subjectMCF-7 Cells
dc.subjectMice
dc.subjectMice, Nude
dc.subjectPaclitaxel
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectSignal Transduction
dc.subjectSirolimus
dc.subjectTOR Serine-Threonine Kinases
dc.subject.classification7 INGENIERÍA Y TECNOLOGÍA
dc.titleColocalized delivery of rapamycin and paclitaxel to tumors enhances synergistic targeting of the PI3K/Akt/mTOR pathway
dc.typeConferencia
dc.identifier.volume22
dc.identifier.issue7
dc.identifier.startpage1310
dc.identifier.endpage1319
refterms.dateFOA2018-10-18T20:12:51Z


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