BODIPY-Lipit Bileşiğinden Yeni Lipozomların Sentezi ve PDT Özelliklerinin Araştırılması

Yıl 2024, Cilt: 2 Sayı: 1, 24 - 35, 24.06.2024

Muhammed Emre Özler , Yasemin Bozkurt , Fazlı Sözmen

Öz

Kemoterapi, radyoterapi, cerrahi müdahale gibi geleneksel kanser tedavi yöntemlerinin yüksek toksisite, ilaç direnci ve enfeksiyon gibi çeşitli yan etkilerinden dolayı, fotodinamik terapi (PDT), fototermal terapi (PTT) veya sonodinamik terapi (STT) gibi invaziv olmayan nispeten daha az yan etkilere sahip kanser tedavi yöntemlerine olan ilgi giderek artmaktadır. Bu non-invaziv terapi yöntemleri içerisinde de PDT sahip olduğu özelliklerinden dolayı literatürde en çok çalışılan terapi yöntemlerinden biridir. Bu ve benzeri terapi yöntemleri çalışılırken göz önünde bulundurulması gereken en önemli hususlardan biri fizyolojik koşullardır. Bu nedenle yapı bakımından hücre zarına benzeyen lipozomal yapılar ilaç taşıyıcı sistemler başta olmak üzere yaygın bir şekilde araştırılmaktadırlar. Genellikle nano boyutta sentezlenen lipozomal yapılar kolloidal kararlılıkları, biyouyumlu olmaları, toksik olmamaları ve etkili bir şekilde hedeflenebilmeleri gibi özellikleri nedeniyle de son derece ilgi görmektedirler. Bu çalışmada PDT özelliğine sahip BODIPY bazlı yeni lipozomal yapıların sentezlenmesi amaçlanmıştır. Bu amaçla, öncelikle BODIPY türevi bir bileşik fotoduyarlaştırıcı olarak sentezlenip karakterize edilmiştir. Daha sonra, serbest karboksil grubu içeren bu BODIPY (4,4-Difloro-4-bora-3a, 4a-diaza-s-indasen) türevi, lizofosfatidilkolin ile esterleşme reaksiyonu vasıtasıyla konjuge edilmiştir. Elde edilen BODIPY-Lipit konjugatı kullanılarak ince film hidratlama yöntemiyle nano boyutta lipozomal yapılar sentezlenmiştir. Son olarak yapılarında bir fotoduyarlaştırıcı bileşik bulunduran bu lipozomal yapıların PDT özellikleri 530 nm dalga boyundaki LED ışığı kullanılarak belirlenmiştir.

Anahtar Kelimeler

BODIPY, Fotodinamik Terapi, Lipozom

Destekleyen Kurum

TÜBİTAK

Proje Numarası

121Z810

Teşekkür

Bu çalışmayı 121Z810 numaralı proje kapsamında destekleyen TÜBİTAK’a teşekkür ederiz.

Synthesis of New Liposomes from BODIPY-Lipid Compound and Investigation of PDT Properties

Öz

Due to the various side effects of traditional cancer treatment methods such as chemotherapy, radiotherapy and surgical intervention, such as high toxicity, drug resistance and infection, non-invasive methods such as photodynamic therapy (PDT), photothermal therapy (PTT) or sonodynamic therapy (STT) have relatively fewer side effects and interest for them in these cancer treatment methods is increasing. Among these non-invasive therapy methods, PDT is one of the most researched therapy methods in the literature due to its features. One of the most important issues to consider when researching this and similar therapy methods is physiological conditions. For this reason, liposomal structures, which are resemble in structure to the cell membrane, are widely researched, primarily as drug delivery systems. Liposomal structures, which are generally synthesized in nanoscale, attract great attention due to their colloidal stability, biocompatibility, non-toxicity and are effective targeted. In this study, it was aimed to synthesize new BODIPY-based liposomal structures with PDT properties. For this purpose, firstly, a BODIPY-derived compound was synthesized and characterized as a photosensitizer. Then, via an esterification reaction, this BODIPY derivative which had a free carboxyl group was conjugated with lysophosphatidylcholine. Nanoscale liposomal structures were synthesized by the thin film hydration method using the obtained BODIPY-Lipid conjugate. Finally, utilizing LED light with a wavelength of 530 nm, the PDT characteristics of these liposomal structures which include a photosensitizer component in their structure were determined.

Anahtar Kelimeler

BODIPY, Liposome, Photodynamic Therapy

Proje Numarası

121Z810

Kaynakça

• Abrahamse, H., & Hamblin, M. R. (2016). New photosensitizers for photodynamic therapy. Biochemical Journal, 473(4), 347-364.
• Ambroz, F., Donnelly, J. L., Wilden, J. D., Macdonald, T. J., & Parkin, I. P. (2019) Carboxylic acid functionalization at the meso-position of the bodipy core and its influence on photovoltaic performance. Nanomaterials, 9(10), 1346.
• Cakmak, Y., Kolemen, S., Duman, S., Dede, Y., Dolen, Y., Kilic, B., Kostereli, Z., Tatar Yildirim, L., Dogan, A. L., Guc, D. & Akkaya, E. (2011). Designing excited states: theory-guided access to efficient photosensitizers for photodynamic action.Angewandte Chemie-International Edition, 50(50).
• Cheng, M. H., Harmatys, K. M., Charron, D. M., Chen, J., & Zheng, G. (2019) Stable J-Aggregation of an aza-BODIPY-Lipid in a Liposome for Optical Cancer Imaging. Angewandte Chemie - International Edition, 58(38), 13394–13399.
• Correia, J. H., Rodrigues, J. A., Pimenta, S., Dong, T., & Yang, Z. (2021). Photodynamic therapy review: principles, photosensitizers, applications, and future directions. Pharmaceutics, 13(9), 1332.
• Derycke, A. S., & de Witte, P. A. (2004). Liposomes for photodynamic therapy. Advanced Drug Delivery Reviews, 56(1), 17-30.
• Ion, R. M. (2000). Porphyrins for tumor destruction in photodynamic therapy. Current Topics in Biophysics, 24(1), 21-34.
• Jin, C. S. (2015). Porphyrin-based Nanostructure-Dependent Photodynamic and Photothermal Therapies, PhD Thesis, University of Toronto, Canada.
• Jin, C. S., Lovell, J. F. & Zheng, G. (2013). One minute, sub-one-watt photothermal tumor ablation using porphysomes, intrinsic multifunctional nanovesicles. Journal of Visualized Experiments, (79), 1–6.
• Kamkaew, A., Lim, S. H., Lee, H. B., Kiew, L. V., Chung, L. Y., & Burgess, K. (2013). BODIPY dyes in photodynamic therapy. Chemical Society Reviews, 42(1), 77-88.
• Li, Q., Li, Y., Min, T., Gong, J., Du, L., Phillips, D. L., ... & Tang, B. Z. (2020). Time‐dependent photodynamic therapy for multiple targets: a highly efficient AIE‐active photosensitizer for selective bacterial elimination and cancer cell ablation. Angewandte Chemie, 132(24), 9557-9564.
• Lim, S. H., Thivierge, C., Nowak-Sliwinska, P., Han, J., van den Bergh, H., Wagnieres, G., ... & Lee, H. B. (2010). In vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy. Journal of Medicinal Chemistry, 53(7), 2865–2874.
• Liu, X. Y., Ruan, L. M., Mao, W. W., Wang, J. Q., Shen, Y. Q., & Sui, M. H. (2010). Preparation of RGD-modified long circulating liposome loading matrine, and its in vitro anti-cancer effects. International Journal of Medical Sciences, 7(4), 197–208.
• Lombardo, D., & Kiselev, M. A. (2022). Methods of liposomes preparation: Formation and control factors of versatile nanocarriers for biomedical and nanomedicine application. Pharmaceutics, 14(3), 543.
• Loudet, A., & Burgess, K. (2007). BODIPY dyes and their derivatives: syntheses and spectroscopic properties. Chemical Reviews, 107(11), 4891-4932.
• Lovell, J. F., Jin, C. S., Huynh, E., Jin, H., Kim, C., Rubinstein, J. L., ... & Zheng, G. (2011). Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. Nature Materials, 10(4), 324– 332.
• Niu, C. & Aisa, H. A. (2017). Upregulation of melanogenesis and tyrosinase activity: potential agents for vitiligo. Molecules, 22(8), 1303.
• Nsairat, H., Khater, D., Sayed, U., Odeh, F., Al Bawab, A., & Alshaer, W. (2022). Liposomes: Structure, composition, types, and clinical applications. Heliyon, 8(5).
• Robertson, C. A., Evans, D. H., & Abrahamse, H. (2009). Photodynamic therapy (PDT): a short review on cellular mechanisms and cancer research applications for PDT. Journal of Photochemistry and Photobiology B: Biology, 96(1), 1-8.
• Simões, J. C., Sarpaki, S., Papadimitroulas, P., Therrien, B., & Loudos, G. (2020). Conjugated photosensitizers for imaging and PDT in cancer research. Journal of Medicinal Chemistry, 63(23), 14119-14150.
• Sun, B., Lovell, J. F., & Zhang, Y. (2023). Current development of cabazitaxel drug delivery systems. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 15(2), e1854.
• Treibs, A., & Kreuzer, F. H. (1968). Difluorboryl‐komplexe von di‐und tripyrrylmethenen. Justus Liebigs Annalen der Chemie, 718(1), 208-223.
• Watson, H. (2015). Biological membranes. Essays in Biochemistry, 59, 43-69.