KANSER İMMÜNOTERAPİSİNDE KULLANILMAK ÜZERE PHBHHX BAZLI KATI LİPİD NANOPARTİKÜL DİZAYNI

Year 2020, , 239 - 248, 30.07.2020

Nelisa Laçin Türkoğlu

https://doi.org/10.18036/estubtdc.583152

Abstract

Kanser tedavisinde immünoterapi yaklaşımının kullanılması her geçen gün popüleritisini arttırarak bu alanda yerini sağlamlaştırmaktadır. Mevcut kanser immünoterapi sistemleri ile yapılan tedaviler tek başına istenen verimlilikte çalışmamaktadır. İlgili alanda terapötik maddelerin tümöre iletilmesi için oldukça karmaşık ve sınırlayıcı olan tümör mikroçevresini aşarak tümör hücresine iletilmesi gerekmektedir. Bu çalışmada, IL-6 kodlayan plazmid DNA model olarak kullanılarak, plazmidi tümör hücrelerine aktarabilecek bir taşıyıcı sisteminin geliştirilmesi üzerine odaklanılmıştır. Farklı miktarlarda bileşenler kullanılarak ve farklı koşullarda çözücü difüzyon yöntemiyle bir katı lipit katyonik nanopartikül sisteminin üretimi hedeflenmiştir. Elde edilen nanotaşıyıcının kimyasal yapısı ATR-FTIR spektroskopisi ile karakterize edilmiştir. Zeta-sizer cihazı kullanılarak, nanopartiküllerin ortalama büyüklüğünün 208,1 nm (± 256,8) [Polidispersite Endeksi (PDI), 0,06] ve 13,7 mV (± 5,4) zeta potansiyeline sahip olduğu tespit edilmiştir. Nanopartiküllerin morfolojik karakterizasyonu taramalı elektron mikroskobu (SEM), atomik kuvvet mikroskobu (AFM) cihazları ile incelenmiştir. PHBHHX bazlı SLN'nin sitotoksisitesi, fare fibroblast hücre hattında (L929) MTT testi ile belirlenmiştir. PHBHHX bazlı nanopartikül, yeşil floresan protein (GFP) ve IL-6 kodlayan plazmid DNA ile konjuge edildikten sonra MCF-7 hücrelerine transfeksiyonu gerçekleştirilip, transfeksiyon verimi GFP ekspresyonunu floresan mikroskobu ile takip edilmesi ile belirlenmiştir. GFP ekspresyon etkinliği %73 (± 5,8) olarak belirlenmiştir. 

Keywords

İmmünoterapi, Nanotaşıyıcı, IL-6, GFP

References

• Barbaros, MB, Dikmen, M. 2015. Kanser Immünoterapisi. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, 31(4):177-182.
• Beer C, Foldbjerg R, Hayashi Y, Sutherland DS, Autrup H, 2012. Toxicity of silver nanoparticles—nanoparticle or silver ion. Toxicology letters, 208(3): 286-292.
• Brigger I, Dubernet C, Couvreur P, 2012. Nanoparticles in cancer therapy and diagnosis. Advanced drug delivery reviews, 64:24-36.
• Büyükköroğlu, G. (2016). Development of Solid Lipid Gene Delivery System. Turkish Journal of Pharmaceutical Sciences, 13(2): 249-258.
• del Pozo-Rodríguez A, Delgado D, Solinís MA, Gascón AR, Pedraz, JL, 2007. Solid lipid nanoparticles: formulation factors affecting cell transfection capacity. International journal of pharmaceutics, 339(1-2):261-268.
• Foldbjerg R, Olesen P, Hougaard M, Dang DA, Hoffmann HJ, Autrup H, 2009. PVP-coated silver nanoparticles and silver ions induce reactive oxygen species, apoptosis and necrosis in THP-1 monocytes. Toxicology Letters, 190:156–162.
• Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK, 2018. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nature reviews Clinical oncology, 15(5): 325.
• Güven, GU, Laçin, NT, Pişkin E, 2008. Monosize polycationic nanoparticles as non‐viral vectors for gene transfer to HeLa cells. Journal of tissue engineering and regenerative medicine, 2(2‐3): 155-163.
• Huang Y, Li D, Qin DY, Gou HF, Wei W, Wang YS, Wang W, 2018. Interleukin-armed chimeric antigen receptor-modified T cells for cancer immunotherapy. Gene therapy, 25(3): 192.
• Kılıçay E, Demirbilek M, Türk M, Güven E, Hazer B, Denkbas EB, 2011. Preparation and characterization of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate)(PHBHHX) based nanoparticles for targeted cancer therapy. European Journal of Pharmaceutical Sciences, 44(3):310-320.
• Lee S, Margolin K, 2011. Cytokines in cancer immunotherapy. Cancers, 3(4):3856-3893.
• Lin G, Zhang H, Huang L, 2015. Smart polymeric nanoparticles for cancer gene delivery. Molecular pharmaceutics, 12(2): 314-321.
• Navarro E, Piccapietra F, Wagner B, Marconi F, Kaegi R, Odzak N, Sigg L, Behra R, 2008. Toxicity of silver nanoparticles to Chlamydomonas reinhardtii. Environmental Science & Technology, 42: 8959–8964.
• Olbrich C, Bakowsky U, Lehr CM, Müller RH, Kneuer C, 2001. Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA. Journal of controlled release, 77(3): 345-355
• Pal SL, Jana U, Manna PK, Mohanta GP, Manavalan R, 2011. Nanoparticle: An overview of preparation and characterization. Journal of Applied Pharmaceutical Science, 1(6): 228-234.
• Riley RS, June CH, Langer R, Mitchell MJ, 2019. Delivery technologies for cancer immunotherapy. Nature Reviews Drug Discovery, 1.
• Rosenberg SA, 1988. Immunotherapy of cancer using interleukin 2: current status and future prospects. Immunology Today, 9(2):58-62.
• Rosenberg SA, Yang JC, Restifo NP, 2004. Cancer immunotherapy: moving beyond current vaccines. Nature medicine, 10(9): 909.
• Sun M, Zhou P, Pan LF, Liu S, Yang HX, 2009. Enhanced cell affinity of the silk fibroin-modified PHBHHx material. Journal of Materials Science: Materials in Medicine, 20(8): 1743-1751.
• Sunshine, JC, Sunshine SB, Bhutto I, Handa JT, Green JJ. 2012. Poly (β-amino ester)-nanoparticle mediated transfection of retinal pigment epithelial cells in vitro and in vivo. PloS one, 7(5): e37543.
• Thomas M, Klibanov AM, 2003. Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells. Proceedings of the National Academy of Sciences, 100(16): 9138-9143.
• Wang EC, Wang AZ, 2013. Nanoparticles and their applications in cell and molecular biology. Integrative Biology, 6(1): 9-26.
• Xi, J., Kong L, Gao Y, Gong Y, Zhao N, Zhang, X, 2005. Properties of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) films modified with polyvinylpyrrolidone and behavior of MC3T3-E1 osteoblasts cultured on the blended films. Journal of Biomaterials Science, Polymer Edition, 16(11), 1395-1408.
• Xu Z, Chen L, Gu W, Gao Y, Lin L, Zhang Z, Li Y, 2009. The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma. Biomaterials, 30(2): 226–232.
• Yang HX, Sun M, Zhang Y, Zhou P, 2011. Degradable PHBHHx modified by the silk fibroin for the applications of cardiovascular tissue engineering. ISRN Materials Science, 2011.
• Yu Y, Cui J, 2018. Present and future of cancer immunotherapy: A tumor microenvironmental perspective. Oncology letters, 16(4):4105-4113.
• Zarogoulidis P, Lampaki S, Yarmus L, Kioumis I, Pitsiou G, Katsikogiannis N, Organtzis J, 2014. Interleukin-7 and interleukin-15 for cancer. Journal of Cancer, 5(9):765.
• Zhang H, Chen J, 2018. Current status and future directions of cancer immunotherapy. Journal of Cancer, 9(10):1773.
• Zhang T, Chen J, Zhang Y, Shen Q, Pan W, 2011a. Characterization and evaluation of nanostructured lipid carrier as a vehicle for oral delivery of etoposide. European Journal of Pharmaceutical Sciences, 43:174–179.