Ufuk GÜNDÜZ
(Orta Doğu Teknik Üniversitesi, Fen-Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Ankara, Türkiye)
Proje Grubu: TÜBİTAK KBAG ProjeSayfa Sayısı: 57Proje No: 214Z180Proje Bitiş Tarihi: 15.03.2016Türkçe

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Poli-Amidoamin (PAMAM) Dendrimer ile Modifiye Edilmis Manyetik Nanoparçacıkların Sentezlenmesi ve Meme Kanser Hücrelerine CpG Oligodeoksinükleotit Tasıma Amacı ile Uygulanması
Kanser tedavisindeki nanoteknolojik uygulamalardan en önemlisi kanser hücrelerine ilaç, oligonükleotit ve gen tasımak için üretilen nanoparçacıklardır. Nanoparçacıklar tümör hücrelerini hedefleyip öldürürken, saglıklı dokulara en az düzeyde zarar verecek sekilde tasarlanmalıdır. Bu çalısmada CpG oligodeoksinükleotiti uygun ve etkili bir sekilde tümör hücrelerine tasıması için CpG-ODN ile etkilesime giren nanoparçacıkların gelistirilmesi amaçlanmıstır. CpGODN? ler hücre ölümü için sinyal kaskadını olusturan Toll benzeri reseptör 9?u (TLR9) uyarmaktadır. Bu çalısmada Fe3O4 manyetik çekirdek, aminoasilan (APTS) ara katmanı ve katyonik poli-amidoamin (PAMAM) dendrimerden olusan üç katmanlı manyetik nanoparçacıklar sentezlenmistir. Sonuçlar DcMNP?lerin fonksiyonel grupları, simetri mükemmelligi, boyut dagılımı, manyetik özelligi ve toksik olmaması açısından hedeflenmis kanser tedavisinde ilaç tasıyıcı olarak kullanılabilecegini göstermistir. CpG-ODN?lerin, çesitli engelleri asarak tümör bölgesine basarılı bir sekilde tasınması etkili bir tasıyıcı vektörün kullanılmasına baglıdır. Çünkü CpG-ODN?ler serumdaki nükleazlar tarafından hızlı bir sekilde yıkıma ugrayabilir ve hücre zarından difüzyonla geçemeyebilirler. Bu çalısmanın ikinci kısmında, CpG-ODN?ler yeni nesil bir polimer olan ve basarılı bir sekilde sentezlenen DcMNP?lerin yüzeyine etkili bir sekilde baglanmıs ve manyetik alan varlıgında tümör bölgesine hedeflenmistir. CpG-ODN?nin, DcMNP?nin yüzeyine baglandıgı agaroz jel elektroforezi, UV spektrofotometre, zeta potansiyel ve XPS analizleri ile belirlenmistir. Daha sonra, TEM ve SEM görüntülerinden sentezlenen dendrimer kaplı manyetik nanoparçacıkların (DcMNPs) boyut bakımından uniform karakterde ve ortalama 40±10 nm çapa sahip oldukları görülmüstür. MDA-MB231, SKBR3 ve MCF7 hücre hatlarında, hücre çogalma analizi ile yapılarak konjüge nanoparçacıklar için sitotoksisite belirlenmistir. Sonuçlar sentezlenen DcMNP?lerin yüzeyinde çok miktarda pozitif yük bulundurması sebebiyle meme kanseri dokusunda hücre ölümüne sebep olan CpG-ODN molekülleri ile etkili sekilde elektrostatik etkilesime girdigini; bu nedenle de hedeflenmis kanser tedavisinde CpG-ODN tasımak için uygun bir tasıyıcı olabilecegini göstermistir. Bu nanoparçacıklardaki manyetik çekirdek sayesinde harici manyetik alan kullanılarak ilaçların istenilen bölgeye hedeflenmesi saglanabilmektedir.
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