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

Abstract

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.

Keywords

• BODIPY
• Liposome
• Photodynamic Therapy

BODIPY-Lipit Bileşiğinden Yeni Lipozomların Sentezi ve PDT Özelliklerinin Araştırılması

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

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