Anadolu arısı (Apis mellifera anatoliaca) zehrinin nano-taşıyıcı sistemlere konjugasyonu ve biyoaktivite etklinliğinin belirlenmesi
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Dosyalar
Tarih
2021
Yazarlar
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Yayıncı
Ege Üniversitesi, Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Bal arısı zehri, içerdiği çeşitli aktif bileşenler ile birçok hastalıkta olumlu etkileri bildirilen bir zehirdir. Terapötik etkinliğinin genellikle içerdiği litik, nörotoksin vb. özelliklere sahip peptidlerden ve enzimlerden kaynaklandığı düşünülmektedir. Kanserin günümüz büyük problemlerinden biri olması, yeni tedavi arayışları ile son yıllarda arı zehrinin de kanser üzerindeki çalışmaları ilgi odağı olmuş ve etkili olabileceği gösterilmiştir. Biyomoleküllerin kararsız yapıları ve zehrin oluşturabileceği yan etkiler kullanımlarını kısıtlayabilir. Nanotaşıyıcılar, bu dezavantajların üstesinden gelmek için umut vadeden yaklaşımlar sunar. Mezoporlu silika nanopartiküller (MSN), biyouyumlulukları, porlarının sağladığı yükleme kapasitesi, kimyasal ve biyolojik stabiliteleri sebebiyle ve tümöre ulaşabilme kabiliyetleri ile biyomoleküllerin taşınması için avantajlıdırlar. Ayrıca fonksiyonelleştirilebilir yüzey kimyası diğer nanopartiküler sistemlere göre kanserin tedavisinde MSN'leri öne çıkarmıştır. Bu sebeplerle, arı zehrinin potansiyel antikanser etkisinin mezoporlu silika nanopartiküllere yüklenerek arttırılması sağlanabilir. Çalışma kapsamında, floresan etiketli mezoporlu silika nanopartiküller sentezlendi, karakterizasyonları yapıldı. Nanoboyutlu MSN'lere zehir peptidleri yüklendi. Ham zehrin ve zehir yüklü MSN'lerin etkinlikleri MDA-MB 231 (insan meme adenokarsinoma), PC3 (insan prostat adenokarsinoma), HeLa (insan serviks adenokarsinoma) kanser hücreleri üzerinde, biyouyumlulukları, sağlıklı insan hücre hatları CCD34-Lu (insan sağlıklık akciğer fibroblast hücresi), tümörojenik olmayan HEK-293 (insan embriyonik böbrek hücreleri) üzerinde araştırıldı. MSN'lerin içerdiği floresan etiketi sayesinde, zehir peptidlerinin PC3 ve MDA-MB 231 hücrelerinin içine taşınıp taşınmadığı floresan mikroskopi ve akış sitometri ile araştırıldı. Tümör hücrelerinde genellikle istenen apoptotik etki akış sitometri ile incelendi. Ardından mitokondrinin hücre metabolizması ve apoptozu düzenlemedeki rolleri sebebiyle, arı zehri ve zehir MSN kombinasyonlarının mitokondriyal membran potansiyeline etkileri incelendi. Sonuç olarak, arı zehri ve ülkemizde yetişen arı türü Apis mellifera anatoliaca zehri kanserin maliyetli, ciddi yan etkilere sebep olan ve kanserin direnç geliştirdiği tedavilere ekonomik, kolay ulaşılabilir, yenilikçi tedavi seçeneklerinin sunulması potansiyeline sahiptir. MSN'lerin zehir peptidlerinin, prostat kanseri üzerindeki apoptotik etkisini arttırarak, etkin bir kanser tedavisi sağlayabileceği gösterilmiştir. MSN ve zehir birlikteliği sadece prostat kanseri değil çok çeşitli kanser türleri üzerinde etkili olabilecek potansiyele sahiptir.
Previous studies show that honey bee venom is a venom with various active ingredients and positive effects in many diseases. Its therapeutic efficacy is generally thought to be due to the peptides and enzymes it contains, which have lytic, neurotoxin, etc. properties. The fact that cancer is one of the major problems of our time, the search for new treatments has increased the studies of bee venom on cancer in recent years and it has been shown that it can be effective. The highly laible nature of biomolecules and the side effects of the venom may limit their use. Mesoporous silica nanoparticles (MSNs) arose as promising drug delivery platforms because of their outstanding biocompatibility, their loading capacity provided by their pores, their great chemical and biological robustness, and their ability to reach tumors. In addition, functionalizable surface chemistry has highlighted MSNs in the treatment of cancer over other nanoparticulate systems. For these reasons, the potential anticancer effect of bee venom can be increased with mesoporous silica nanoparticles as drug delivery systems. In the present study, fluorescently labeled mesoporous silica nanoparticles were synthesized and characterization studies were carried out. Venom peptides were loaded into nanosized MSNs. The cytotoxicity of venom and venom-loaded MSNs were determined on MDA-MB 231 (human breast adenocarcinoma), PC3 (human prostate adenocarcinoma), HeLa (human cervical adenocarcinoma) cancer cells, and their biocompatibility were investigated on HEK-293 (human embryonic kidney) and CCD34-Lu (normal human lung fibroblast) normal cell lines. With the fluorescent label contained in MSNs, it was investigated by fluorescence microscopy and flow cytometry whether the venom peptides were transported into PC3 and MDA-MB 231 cells. The generally desired apoptotic effect on tumor cells was examined by flow cytometry. After that, the effects of bee venom and venom MSN combinations on mitochondrial membrane potential were examined because of the important roles of mitochondria in regulating cell metabolism and apoptosis. In conclusion, bee venom and the venom of Apis mellifera anatoliaca grown in our country have the potential to offer cost-effective, easily accessible, and innovative treatment options for treatments of cancers that cause costly, serious side effects, and cancer resistance.MSNs can provide an effective cancer treatment with an increased apoptotic effect on prostate cancer by increasing the effects of venom peptides. Venom-loaded MSNs have the potential to affect not only prostate cancer but also a wide variety of cancer types.
Previous studies show that honey bee venom is a venom with various active ingredients and positive effects in many diseases. Its therapeutic efficacy is generally thought to be due to the peptides and enzymes it contains, which have lytic, neurotoxin, etc. properties. The fact that cancer is one of the major problems of our time, the search for new treatments has increased the studies of bee venom on cancer in recent years and it has been shown that it can be effective. The highly laible nature of biomolecules and the side effects of the venom may limit their use. Mesoporous silica nanoparticles (MSNs) arose as promising drug delivery platforms because of their outstanding biocompatibility, their loading capacity provided by their pores, their great chemical and biological robustness, and their ability to reach tumors. In addition, functionalizable surface chemistry has highlighted MSNs in the treatment of cancer over other nanoparticulate systems. For these reasons, the potential anticancer effect of bee venom can be increased with mesoporous silica nanoparticles as drug delivery systems. In the present study, fluorescently labeled mesoporous silica nanoparticles were synthesized and characterization studies were carried out. Venom peptides were loaded into nanosized MSNs. The cytotoxicity of venom and venom-loaded MSNs were determined on MDA-MB 231 (human breast adenocarcinoma), PC3 (human prostate adenocarcinoma), HeLa (human cervical adenocarcinoma) cancer cells, and their biocompatibility were investigated on HEK-293 (human embryonic kidney) and CCD34-Lu (normal human lung fibroblast) normal cell lines. With the fluorescent label contained in MSNs, it was investigated by fluorescence microscopy and flow cytometry whether the venom peptides were transported into PC3 and MDA-MB 231 cells. The generally desired apoptotic effect on tumor cells was examined by flow cytometry. After that, the effects of bee venom and venom MSN combinations on mitochondrial membrane potential were examined because of the important roles of mitochondria in regulating cell metabolism and apoptosis. In conclusion, bee venom and the venom of Apis mellifera anatoliaca grown in our country have the potential to offer cost-effective, easily accessible, and innovative treatment options for treatments of cancers that cause costly, serious side effects, and cancer resistance.MSNs can provide an effective cancer treatment with an increased apoptotic effect on prostate cancer by increasing the effects of venom peptides. Venom-loaded MSNs have the potential to affect not only prostate cancer but also a wide variety of cancer types.
Açıklama
Anahtar Kelimeler
Arı Zehri, Apis Mellifera Anatoliaca, Mezoporlu Silika Nanopartikül, Anti-Kanser Biyomolekül, Mezoporlu Silika Nanopartikül, Bee Venom, Apis Mellifera Anatoliaca, Anti-Cancer Biomolecule, Mesoporous Silica Nanoparticles
