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Administation av cytostatika innehållande liposomer till makrofager
Malmö University, Faculty of Health and Society (HS).
2018 (Swedish)Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
Abstract [sv]

För närvarande är immunreaktiviteten mot egna tumörer låg och forskning pågår för att kunna förstå de bakomliggande mekanismerna. Djupare kunskap om hur tumörassocierade makrofager (TAM) interagerar med såväl tumör och stromaceller som med celler inom det adaptiva immunförsvaret kommer att kunna förändra diagnosen för patienter med tumörer. Syftet med denna studie är att undersöka om toxicitet kan uppnås hos makrofager genom liposomal administration av cytostatikan Temozolomide (TMZ). Cellinjerna THP-1 Raw264.7 inkuberades med olika koncentrationer av fritt samt liposomalt TMZ och analyserades med MTT-analys i kombination med flödescytometri och LDH-analys respektive. Humana monocyter isolerades från givare och differentierades till makrofager samt M2 makrofager. Av de isolerade och differentierade cellerna analyserades monocyter, makrofager och macrophage-colony stimulating factor (M-CSF) samt IL-4 behandlade M2 differentierade makrofager efter inkubering med fritt samt liposomalt TMZ. TMZ påverkade inte vitalitet eller proliferation hos THP-1 celler. Raw264.7 visade en känslighet efter inkubation med olika koncentrationer av fritt TMZ. Humana monocyter, makrofager och M2 differentierade makrofager visade inte tydliga resultat som dessutom varierade mellan olika givare. Fler tester på humana mononukleära celler föreslås med liposomer innehållande högre koncentration TMZ samt fri TMZ i koncentrationer upp till 40 µg/ml. Tester av ytterligare cytotoxiska substanser utöver TMZ kan leda till upptäckten av en effektivare toxicitets administrator för makrofager. Nyckelord: Liposomal, administration, makrofager, Temozolomide, toxicitet

Abstract [en]

In the human population immune reactivity against tumor cells is low and research is currently conducted to understand the underlaying mechanism. With a deeper understanding of how tumor-associated macrophages interact with tumor and stromal cells as well as the adaptive immune cells the diagnose of tumor patients will change. This study aimed to investigate if selective toxicity against macrophages can be achieved by liposomal administration of the chemotherapeutic drug Temozolomide (TMZ). The cell lines THP-1 and Raw264.7 were incubated with different concentrations, free as well as liposomal TMZ and analyzed by the MTT-assay in combination with flowcytometry and LDH-assay respectively. Human mononuclear cells where isolated from blood donors and differentiated into M2 macrophages. From these cells monocytes, macrophages and macrophage-colony stimulating factor (M-CSF) with IL-4 treated M2 differentiated macrophages were incubated with free as well as liposomal TMZ. TMZ does not affect the vitality or porliferation of THP-1 cells. Raw264.7 showed sensitivity when incubated with different concentrations of free TMZ. Test results for human mononuclear cells gave unclear results that varied between blood donors. Further tests on human mononuclear cells with liposomes containing higher concentrations of TMZ as well as more tests with free TMZ in concentrations up to 40 µg/ml is suggested. Testing other cytotoxic agents could reveal more effective cytotoxicity administators for macrofages. Keywords: Liposomal, administration, macrophage, Temozolomide, toxicity

Place, publisher, year, edition, pages
Malmö universitet/Hälsa och samhälle , 2018. , p. 20
Keywords [sv]
liposomal, administation, Temozolomide, makrofager, toxicitet
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:mau:diva-25297Local ID: 24781OAI: oai:DiVA.org:mau-25297DiVA, id: diva2:1486805
Educational program
HS Biomedicinsk laboratorievetenskap
Supervisors
Examiners
Available from: 2020-11-03 Created: 2020-11-03Bibliographically approved

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CiteExportLink to record
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