MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI

Aydan Fülden AĞAN, (Düzce Üniversitesi, Arıcılık Araştırma Geliştirme ve Uygulama Merkezi (DAGEM), Düzce, Türkiye)
Meral KEKEÇOĞLU (Düzce Üniversitesi, Fen-Edebiyat Fakültesi, Biyoloji Bölümü, Konuralp, Düzce, Türkiye)
Uludağ Arıcılık Dergisi
10 3
Yıl: 2020 Cilt: 20 Sayı: 2 Sayfa Aralığı: 221 - 231 Metin Dili: Türkçe DOI: 10.31467/uluaricilik.784365 İndeks Tarihi: 23-06-2021

MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI

Öz:
Kanser, insan sağlığını tehdit eden en önemli sağlık sorunlarından birisi olmaya devam etmektedir. Günümüzde kanser hastalığını tedavilerinde cerrahi yöntemler, kemoterapi, radyoterapi, immunoterapi, kanser aşıları gibi yöntemler kullanılmaktadır. Ancak başta kemoterapi olmak üzere bu tedavi yöntemlerinin bazı yan etkilere neden olması, doğal ürünlere olan ilgiyi arttırmıştır. Arı zehrinin peptit bileşenlerinden biri olan melittin, kanser tedavisinde kullanılan en önemli etken maddelerinin başında gelir. Melittinin anti-kanser etkinliği daha önce yapılan araştırmalarla çeşitli kanser türlerinin tedavisinde pre-klinik olarak test edilmiştir. Ancak bu pre-klinik sonuçların kliniğe uygulanabilmesi için, başta melittinin neden olduğu hemolitik aktivite, spesifik olmayan toksisite ve bozunma gibi sorunların üstesinden gelinmelidir. Bu amaçla melittinin çeşitli nanopartiküller ile bir araya getirilerek, melittinin kanserli hücreyi hedefleyebileceği platformlar sunulmuştur. Bu derlemede, henüz çok güncel ve halen geliştirilmekte olan arı zehri bileşenlerinin çeşitli kanser türlerinin tedavisine yönelik in-vitro ve in-vivo uygulamalarına dair mevcut literatür, nanoteknolojik uygulamalar açısından bir araya getirilmiştir.
Anahtar Kelime:

Melittin and Cancer Treatment: Nanotechnological Perspective

Öz:
Cancer continues to be one of the most important health problems threatening human health. Recently, methods such as surgical methods, chemotherapy, radiotherapy, immunotherapy, cancer vaccines are used in the treatment of cancer. However, the fact that these treatment methods, especially chemotherapy, cause some side effects, the interest in natural products has incrased. Melittin, one of the peptide components of bee venom, is one of the most important active ingredients used in cancer treatment. The anti-cancer efficacy of Melittin has been pre-clinically tested in treatment of various types of cancer with previous research. However, in order for these pre-clinical results to be applied to the clinic, problems such as hemolytic activity caused by melittin primarily, nonspecific toxicity and degradation should be overcome. In this review, the current literature on the in-vitro and in-vivo applications of bee venom components for the treatment of various cancer types, which are very current and still under development, are brought together in terms of nanotechnological applications.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık
  • Aliyazicioglu, R. 2019. Therapeutic Effects of Bee Venom. Chemical Science International Journal, 26(1), 1–5. https://doi.org/10.9734/csji/2019/v26i130078.
  • Banks, B. E. C., Brown, C., Burgess, G. M., Burnstock, G., Claret, M., Cocks, T. M., ve Jenkinson, D. H. 1979. Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Nature, 282(5737), 415–417. https://doi.org/10.1038/282415a0.
  • Barrajón-Catalán, E., Menéndez-Gutiérrez, M. P., Falco, A., Carrato, A., Saceda, M., ve Micol, V. 2010. Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level. Cancer Letters, 290(2), 192–203. https://doi.org/10.1016/j.canlet.2009.09.010.
  • Bei, C., Bindu, T., Remant, K. C., ve Peisheng, X. 2015. Dual secured nano-melittin for the safe and effective eradication of cancer cells. J. Mater. Chem. C, 3(1), 25–29. https://doi.org/10.1039/b000000x.
  • Billingham, M. E. J., Morley, J., Hanson, J. M., Shipolini, R. A., ve Vernon, C. A. 1973. An Anti- Inflammatory peptide from bee venom. Nature, 245(5421), 163–164. https://doi.org/10.1038/245163a0.
  • Biniecka, P., Bugajska, Ż., Daniluk, K., ve Jaworski, S. 2017. Carbon nanoparticles as transporters of melittin to glioma grade IV U87 cells in in vitro model. Annals of Warsaw University of Life Sciences - SGGW - Animal Science, 56(1), 23–32. https://doi.org/10.22630/aas.2017.56.1.3.
  • Chen, J., ve Lariviere, W. R. 2010. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword. Progress in Neurobiology, C. 92, ss. 151–183. https://doi.org/10.1016/j.pneurobio.2010.06.00 6.
  • Chen, S. Y., Zhou, P., ve Qin, Y. 2018. Treatment of Rheumatoid Arthritis by Bee-venom Acupuncture. Zhen ci yan jiu = Acupuncture research, 43(4), 251–254. https://doi.org/10.13702/j.1000-0607.170506.
  • Choi, K. E., Hwang, C. J., Gu, S. M., Park, M. H., Kim, J. H., Park, J. H., Hong, J. T. 2014. Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. Toxins, 6(8), 2210–2228. https://doi.org/10.3390/toxins6082210.
  • Daniluk, K., Kutwin, M., Grodzik, M., Wierzbicki, M., Strojny, B., Szczepaniak, J., ve Sosnowska, M. 2019. Use of Selected Carbon Nanoparticles as Melittin. 1–20.
  • Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., … Bray, F. 2015. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer, 136(5), E359–E386. https://doi.org/10.1002/ijc.29210.
  • Frankish, H. 2003. 15 million new cancer cases per year by 2020, says WHO. The Lancet, 361, 1278. https://doi.org/10.1038/nm862.
  • Gajski, G., ve Garaj-Vrhovac, V. 2008. Genotoxic potential of bee venom (Apis Mellifera) on human peripheral blood lymphocytes in vitro using single cell gel electrophoresis assay. Journal of Environmental Science and Health- Part A Toxic/Hazardous Substances and Environmental Engineering, 43(11), 1279– 1287.
  • Gajski, G., ve Garaj-Vrhovac, V. 2010. Increased frequency of sister chromatid exchanges and decrease in cell viability and proliferation kinetics in human peripheral blood lymphocytes after in vitro exposure to whole bee venom. Journal of Environmental Science and Health - Part A Toxic/Hazardous Substances and Environmental Engineering, 45(12), 1654–1659. https://doi.org/10.1080/10934529.2010.50614 4.
  • Gajski, G., ve Garaj-Vrhovac, V. 2011. Bee venom induced cytogenetic damage and decreased cell viability in human white blood cells after treatment in vitro: A multi-biomarker approach. Environmental Toxicology and Pharmacology, 32(2), 201–211. https://doi.org/10.1016/j.etap.2011.05.004.
  • Gajski, G., Garaj-Vrhovac, V. 2013. Melittin: A lytic peptide with anticancer properties. Environmental Toxicology and Pharmacology, 36(2), 697–705. https://doi.org/10.1016/j.etap.2013.06.009.
  • Gajski, G., ve Garaj-vrhovac, V. 2015. Goran Gajski and Vera Garaj-Vrhovac. 88–98. https://doi.org/10.1080/10934520802177862.c
  • Gevod, V. S. 1984. Melittin and the 8-26 fragment Differences in Ionophoric Properties as Measured by Monolayer Method. 45(June), 1079–1083.
  • Habermann, E. 1972. Bee and wasp venoms. Science,177(4046), 314–322. https://doi.org/10.1126/science.177.4046.314.
  • Hanson, J. M., Morley, J., ve Soria-Herrera, C. 1974. Anti-inflamatuary propery of 401 (MCD peptide), A peptide from the venom of the bee, Apis mellifera (L.). British Journal of Pharmacology, 50(3), 383–392. https://doi.org/10.1111/j.1476- 5381.1974.tb09613.x.
  • Huang, C., Jin, H., Qian, Y., Qi, S., Luo, H., Luo, Q., ve Zhang, Z. 2013. Hybrid melittin cytolytic peptide-driven ultrasmall lipid nanoparticles block melanoma growth in vivo. ACS Nano, 7(7), 5791–5800. https://doi.org/10.1021/nn400683s.
  • Huh, J. E., Baek, Y. H., Lee, M. H., Choi, D. Y., Park, D. S., ve Lee, J. D. 2010. Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR- 2 in LLC-tumor-bearing mice. Cancer Letters, 292(1), 98–110. https://doi.org/10.1016/j.canlet.2009.11.013.
  • Ip, S. W., Liao, S. S., Lin, S. Y., Lin, J. P., Yang, J. S., Lin, M. L., Chung, J. G. 2008. The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. In Vivo, 22(2), 237–246.
  • Jallouk, A. P., Palekar, R. U., Marsh, J. N. M., Pan, H., Pham, C. T. N., Schlesinger, P. H., ve Wickline, S. A. 2017. Delivery of a Protease- Activated Cytolytic Peptide Prodrug by Perfluorocarbon Nanoparticles. Physiology & behavior, 176(3), 139–148. https://doi.org/10.1016/j.physbeh.2017.03.04 0.
  • Jang, M. H., Shin, M. C., Lim, S., Han, S. M., Park, H. J., Shin, I., Kim, C. J. 2003. Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299. Journal Pharmacological Sciences, 91(2), 95–104. https://doi.org/10.1254/jphs.91.95.
  • Jeong, Y. J., Choi, Y., Shin, J. M., Cho, H. J., Kang, J. H., Park, K. K., Chang, Y. C. 2014. Melittin suppresses EGF-induced cell motility and invasion by inhibiting PI3K/Akt/mTOR signaling pathway in breast cancer cells. Food and Chemical Toxicology, 68, 218–225. https://doi.org/10.1016/j.fct.2014.03.022.
  • Jin, H., Zhao, G., Hu, J., Ren, Q., Yang, K., Wan, C., Zou, Z. 2017. Melittin-Containing Hybrid Peptide Hydrogels for Enhanced Photothermal Therapy of Glioblastoma. ACS Applied Materials and Interfaces, 9(31), 25755–25766. https://doi.org/10.1021/acsami.7b06431.
  • Jo, M., Park, M. H., Kollipara, P. S., An, B. J., Song, H. S., Han, S. B., Hong, J. T. 2012a. Anticancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicology and Applied Pharmacology, 258(1), 72–81. https://doi.org/10.1016/j.taap.2011.10.009.
  • Jo, M., Park, M. H., Kollipara, P. S., An, B. J., Song, H. S., Han, S. B., Hong, J. T. 2012b. Anticancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicology and Applied Pharmacology, 258(1), 72–81. https://doi.org/10.1016/j.taap.2011.10.009.
  • Kim, H., Park, S. Y., ve Lee, G. 2019. Potential therapeutic applications of bee venom on skin disease and its mechanisms: A literature review. Toxins, 11(7), 4–6. https://doi.org/10.3390/toxins11070374.
  • Koburova, K. L., Michailova, S. G., Shkenderov, S. V. 1985. Further investigation on the antiinflammatory properties of adolapin bee venom polypeptide. Acta physiologica et pharmacologica Bulgarica, 11(2), 50–55.
  • Kollipara, P. S., Kim, J. H., Won, D., Lee, S. M., Sung, H. C., Chang, H. S., Hong, J. T. 2014. Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB. Archives of Pharmacal Research, 37(3), 379–389. https://doi.org/10.1007/s12272-013-0319-8
  • Kuschner. 2017. Delivery of a Protease-Activated Cytolytic Peptide Prodrug by Perfluorocarbon Nanoparticles. Physiology & behavior, 176(3), 139–148. https://doi.org/10.1016/j.physbeh.2017.03.04 0.
  • Lad, P. J., ve Thomas Shier, W. 1979. Activation of microsomal guanylate cyclase by a cytotoxic polypeptide: Melittin. Biochemical and Biophysical Research Communications, 89(1), 315–321. https://doi.org/10.1016/0006- 291X(79)90980-X.
  • Lai, D., Visser-Grieve, S., ve Yang, X. 2012. Tumour suppressor genes in chemotherapeutic drug response. Bioscience Reports, 32(4), 361– 374. https://doi.org/10.1042/BSR20110125.
  • Le, Q. V., Suh, J., ve Oh, Y. K. 2019. Nanomaterial- Based Modulation of Tumor Microenvironments for Enhancing Chemo/Immunotherapy. AAPS Journal, 21(4). https://doi.org/10.1208/s12248-019-0333-y.
  • Li, B., Gu, W., Zhang, C., Huang, X. Q., Han, K. Q., ve Ling, C. Q. 2006. Growth arrest and apoptosis of the human hepatocellular carcinoma cell line Bel-7402 induced by melittin. Onkologie, 29(8–9), 367–371. https://doi.org/10.1159/000094711.
  • Ling, C. Q., Li, B., Zhang, C., Zhu, D. Z., Huang, X. Q., Gu, W., ve Li, S. X. 2005. Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Annals of Oncology, 16(1), 109–115. https://doi.org/10.1093/annonc/mdi019.
  • Liu, C. C., Yang, H., Zhang, L. L., Zhang, Q., Chen, B., ve Wang, Y. 2014. Biotoxins for cancer therapy. Asian Pacific Journal of Cancer Prevention, 15(12), 4753–4758. https://doi.org/10.7314/APJCP.2014.15.12.47 53.
  • Liu, H., Hu, Y., Sun, Y., Wan, C., Zhang, Z., Dai, X., Lin, Z. Z. 2019. Co-delivery of Bee Venom Melittin and a Photosensitizer with an Organic- Inorganic Hybrid Nanocarrier for Photodynamic Therapy and Immunotherapy. ACS Nano, 56(11), 0–16. https://doi.org/10.22630/aas.2017.56.1.3.
  • Liu, X., Chen, D., Xie, L., ve Zhang, R. 2002. Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in-vitro and growth of murine B16 melanomas in-vivo. Journal of Pharmacy and Pharmacology, 54(8), 1083–1089. https://doi.org/10.1211/002235702320266235.
  • McClements, D. J. 2018. Encapsulation, protection, and delivery of bioactive proteins and peptides using nanoparticle and microparticle systems: A review. Advances in Colloid and Interface Science, 253, 1–22. https://doi.org/10.1016/j.cis.2018.02.002.
  • Misra, S. K., Ye, M., Kim, S., ve Pan, D. 2015. Defined nanoscale chemistry influences delivery of peptido-toxins for cancer therapy. PLoS ONE, 10(6), 1–20. https://doi.org/10.1371/journal.pone.0125908.
  • Moga, M. A., Dimienescu, O. G., Arvǎtescu, C. A., Ifteni, P., ve Pleş, L. 2018. Anticancer activity of toxins from bee and snake venom-an overview on ovarian cancer. Molecules, 23(3), 1–21. https://doi.org/10.3390/molecules23030692.
  • Moon, D. O., Park, S. Y., Heo, M. S., Kim, K. C., Park, C., Ko, W. S., Kim, G. Y. 2006. Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. International Immunopharmacology, 6(12), 1796–1807. https://doi.org/10.1016/j.intimp.2006.07.027.
  • Moreno, M., ve Giralt, E. 2015. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: Melittin, apamin and mastoparan. Toxins, 7(4), 1126– 1150. https://doi.org/10.3390/toxins7041126.
  • Muhamad, N., Plengsuriyakarn, T., ve Na- Bangchang, K. 2018. Application of active targeting nanoparticle delivery system for chemotherapeutic drugs and traditional/herbal medicines in cancer therapy: A systematic review. International Journal of Nanomedicine, 13, 3921–3935. https://doi.org/10.2147/IJN.S165210.
  • Oršolić, N. 2009. Potentiation of bleomycin lethality in hela and V79 cells by bee venom. Arhiv za Higijenu Rada i Toksikologiju, 60(3), 317–326. https://doi.org/10.2478/10004-1254-60-2009- 1936.
  • Oršolić, N. 2012. Bee venom in cancer therapy. Cancer and Metastasis Reviews, 31(1–2), 173–194. https://doi.org/10.1007/s10555-011- 9339-3.
  • Orsolic, N., Knezevic, A., Sver, L., Terzic, S., Hackenberger, BK., Basic, I. 2003a. Influence of honey bee products on transplantable murine tumours. Veterinary and Comparative Oncology, 1(4), 216–226. https://doi.org/10.1111/j.1476- 5810.2003.00029.x.
  • Oršolić, N., Šver, L., Verstovšek, S., Terzić, S., ve Bašić, I. 2003b. Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom. Toxicon, 41(7), 861–870. https://doi.org/10.1016/S0041- 0101(03)00045-X.
  • Park, M. H., Choi, M. S., Kwak, D. H., Oh, K. W., Yoon, D. Y., Han, S. B., Hong, J. T. 2011. Anticancer effect of bee venomin prostate cancer cells through activation of caspase pathway via inactivation of NF-κB. Prostate, 71(8), 801– 812. https://doi.org/10.1002/pros.21296.
  • Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., ve Langer, R. 2007. Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2(12), 751–760. https://doi.org/10.1038/nnano.2007.387.
  • Phan, N. K. 2014. Biological therapy: a new age of cancer treatment. Biomedical Research and Therapy, 1(2), 32–34. https://doi.org/10.7603/s40730-014-0006-5.
  • Qi, J., Chen, Y., Xue, T., Lin, Y., Huang, S., Cao, S., Lin, Z. 2019. Graphene Oxide Based Magnetic Nanocomposites for Melittin Delivery to Cervical Cancer HeLa Cells. 0–16.
  • Rady, I., Siddiqui, I. A., Rady, M., ve Mukhtar, H. 2017. Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer Letters, 402(608), 16–31. https://doi.org/10.1016/j.canlet.2017.05.010.
  • Raghuraman, H., ve Chattopadhyay, A. 2007. Melittin: A membrane-active peptide with diverse functions. Bioscience Reports, 27(4– 5), 189–223. https://doi.org/10.1007/s10540- 006-9030-z.
  • Riley, M. K., ve Vermerris, W. 2017. Recent advances in nanomaterials for gene delivery-A review. Nanomaterials, 7(5), 1–19. https://doi.org/10.3390/nano7050094.
  • Russell, P. J., Hewish, D., Carter, T., Sterling-Levis, K., Ow, K., Hattarki, M., Kortt, A. A. 2004. Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: In vitro and in vivo studies. Cancer Immunology, Immunotherapy, 53(5), 411–421. https://doi.org/10.1007/s00262-003- 0457-9.
  • Senel, E., Kuyucu, M., ve Süslü, I. 2014. Honey and bee venom in dermatology: A novel possible alternative or complimentary therapy for psoriasis vulgaris. Ancient Science of Life, 33(3), 190. https://doi.org/10.4103/0257- 7941.144626.
  • Siegel, R. L., Miller, K. D., ve Jemal, A. 2016. Cancer statistics, 2016. CA: A Cancer Journal for Clinicians, 66(1), 7–30. https://doi.org/10.3322/caac.21332.
  • Soman, N. R., Baldwin, S. L., Hu, G., Marsh, J. N., Lanza, G. M., Heuser, J. E., Schlesinger, P. H. 2009. Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth. Journal of Clinical Investigation, 119(9), 2830– 2842. https://doi.org/10.1172/JCI38842.
  • Son, D. J., Lee, J. W., Lee, Y. H., Song, H. S., Lee, C. K., ve Hong, J. T. 2007. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacology and Therapeutics, 115(2), 246–270. https://doi.org/10.1016/j.pharmthera.2007.04. 004.
  • Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet- Tieulent, J., ve Jemal, A. 2015. Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 65(2), 87–108. https://doi.org/10.3322/caac.21262.
  • Tu, W. C., Wu, C. C., Hsieh, H. L., Chen, C. Y., ve Hsu, S. L. 2008. Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells. Toxicon, 52(2), 318–329. https://doi.org/10.1016/j.toxicon.2008.06.007.
  • Varanda, E. A., Monti, R., ve Tavares, D. C. 1999. Inhibitory effect of propolis and bee venom on the mutagenicity of some direct-and indirectacting mutagens. Teratogenesis Carcinogenesis and Mutagenesis, 19(6), 403– 413. https://doi.org/10.1002/(SICI)1520- 6866(1999)19:6<403:AID-TCM4>3.0.CO;2-2.
  • Wang, L., Zheng, M., ve Xie, Z. 2018. Nanoscale metal-organic frameworks for drug delivery: A conventional platform with new promise. Journal of Materials Chemistry B, 6(5), 707– 717. https://doi.org/10.1039/c7tb02970e.
  • Wang, X., Xiong, L., Yu, G., Li, D., Peng, T., Luo, D., ve Xu, J. 2015. Cathepsin S silencing induces apoptosis of human hepatocellular carcinoma cells. American Journal of Translational Research, 7(1), 100–110.
  • Wattanakul, K., Imae, T., Chang, W. W., Chu, C. C., Nakahata, R., ve Yusa, S. ichi. 2019. Oligopeptide-side chained alginate nanocarrier for melittin-targeted chemotherapy. Polymer Journal, 51(8), 771–780. https://doi.org/10.1038/s41428-019-0191-6.
  • Wong, R. S. Y. (2011). Apoptosis in cancer: From pathogenesis to treatment. Journal of Experimental and Clinical Cancer Research, 30(1), 87. https://doi.org/10.1186/1756-9966- 30-87.
  • Xiao, J., Duan, X., Yin, Q., Zhang, Z., Yu, H., ve Li, Y. 2013. Nanodiamonds-mediated doxorubicin nuclear delivery to inhibit lung metastasis of breast cancer. Biomaterials, 34(37), 9648–9656. https://doi.org/10.1016/j.biomaterials.2013.08. 056.
  • Yang, L., Cui, F., Shi, K., Cun, D., ve Wang, R. 2009. Design of high payload PLGA nanoparticles containing melittinsodium dodecyl sulfate complex by the hydrophobic ion-pairing technique. Drug Development and Industrial Pharmacy, 35(8), 959–968. https://doi.org/10.1080/03639040902718039.
  • Yezhelyev, M. V., Gao, X., Xing, Y., Al-Hajj, A., Nie, S., ve O’Regan, R. M. 2006. Emerging use of nanoparticles in diagnosis and treatment of breast cancer. Lancet Oncology, 7(8), 657– 667. https://doi.org/10.1016/S1470- 2045(06)70793-8.
  • Zarrinnahad, H., Mahmoodzadeh, A., Hamidi, M. P., Mahdavi, M., Moradi, A., Bagheri, K. P., ve Shahbazzadeh, D. 2018. Apoptotic Effect of Melittin Purified from Iranian Honey Bee Venom on Human Cervical Cancer HeLa Cell Line. International Journal of Peptide Research and Therapeutics, 24(4), 563–570. https://doi.org/10.1007/s10989-017-9641-1.
  • Zhou, T., Zhou, X., ve Xing, D. 2014. Controlled release of doxorubicin from graphene oxide based charge-reversal nanocarrier. Biomaterials, 35(13), 4185–4194. https://doi.org/10.1016/j.biomaterials.2014.01. 044.
APA AĞAN A, kekeçoğlu m (2020). MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. , 221 - 231. 10.31467/uluaricilik.784365
Chicago AĞAN AYDAN FÜLDEN,kekeçoğlu meral MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. (2020): 221 - 231. 10.31467/uluaricilik.784365
MLA AĞAN AYDAN FÜLDEN,kekeçoğlu meral MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. , 2020, ss.221 - 231. 10.31467/uluaricilik.784365
AMA AĞAN A,kekeçoğlu m MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. . 2020; 221 - 231. 10.31467/uluaricilik.784365
Vancouver AĞAN A,kekeçoğlu m MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. . 2020; 221 - 231. 10.31467/uluaricilik.784365
IEEE AĞAN A,kekeçoğlu m "MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI." , ss.221 - 231, 2020. 10.31467/uluaricilik.784365
ISNAD AĞAN, AYDAN FÜLDEN - kekeçoğlu, meral. "MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI". (2020), 221-231. https://doi.org/10.31467/uluaricilik.784365
APA AĞAN A, kekeçoğlu m (2020). MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. Uludağ Arıcılık Dergisi, 20(2), 221 - 231. 10.31467/uluaricilik.784365
Chicago AĞAN AYDAN FÜLDEN,kekeçoğlu meral MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. Uludağ Arıcılık Dergisi 20, no.2 (2020): 221 - 231. 10.31467/uluaricilik.784365
MLA AĞAN AYDAN FÜLDEN,kekeçoğlu meral MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. Uludağ Arıcılık Dergisi, vol.20, no.2, 2020, ss.221 - 231. 10.31467/uluaricilik.784365
AMA AĞAN A,kekeçoğlu m MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. Uludağ Arıcılık Dergisi. 2020; 20(2): 221 - 231. 10.31467/uluaricilik.784365
Vancouver AĞAN A,kekeçoğlu m MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI. Uludağ Arıcılık Dergisi. 2020; 20(2): 221 - 231. 10.31467/uluaricilik.784365
IEEE AĞAN A,kekeçoğlu m "MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI." Uludağ Arıcılık Dergisi, 20, ss.221 - 231, 2020. 10.31467/uluaricilik.784365
ISNAD AĞAN, AYDAN FÜLDEN - kekeçoğlu, meral. "MELİTTİN VE KANSER TEDAVİSİ: NANOTEKNOLOJİK BAKIŞ AÇISI". Uludağ Arıcılık Dergisi 20/2 (2020), 221-231. https://doi.org/10.31467/uluaricilik.784365
Sayfa Oluşturulma Tarihi
23-04-2024 18:35

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