Title Biološki učinci heptametinskih cijaninskih boja Title (english) Biological effects of heptamethine cyanine dyes Author Petra Jadrijević-Mladar Mentor Anamaria Brozović (mentor)Mentor Nada Oršolić (komentor)Committee member Nada Oršolić (predsjednik povjerenstva)Committee member Maja Matulić (član povjerenstva)Committee member Romana Gračan (član povjerenstva)Committee member Domagoj Đikić (član povjerenstva)Granter University of Zagreb Defense date and country 2024-07-15, Croatia Scientific / art field, NATURAL SCIENCES Abstract Heptametinske boje iz skupine cijaninskih boja imaju fluorescentna svojstva i fluoresciraju u bliskom IR-području. Zbog niske fototoksičnost imaju potencijalnu primjenu u dijagnostičke svrhe. Zahvaljujući svojoj fotosenzibilnosti mogu se koristiti i u sklopu fotodinamične terapije pri liječenju pojedinih tipova tumora. Prilikom izrade ovog diplomskog rada ispitivana su biološka svojstva triju cijaninskih boja (Cy7): SB-35, SB-53 i SB-55, novosintetiziranih derivata fenantridina s aminokiselinskim supstituentima (glicin, lizin) i gvanidinokarbonilpirolnom jedinicom. Učinak boja Cy7 na metabolizam stanice, kao mjere vijabilnosti, njihova akumulacija u stanici i fototoksičnost ispitana je korištenjem stanica raka grlića maternice (HeLa), adenokarcinoma alveola (A549), melanoma (RPMI-7951) i normalnih fibroblasta. Moguća selektivnost spojeva s obzirom na otpornost stanica na lijekove ispitana je na dodatne četiri linije stanica: stanice seroznog karcinoma jajnika visokog stupnja (roditeljska MES-OV i linija MES-OV CBP otporna na karboplatinu ) i stanice adenokarcinoma jajnika (roditeljska SK-OV-3 i linija SK-OV-3 CBP otporna na karboplatinu). Korištenjem testa 3-(4,5-metiltiazol-2-il)-2,5-difeniltetrazolium bromid utvrđeno je da slaba citotoksičnost Cy7 boja, ali i selektivnost s obzirom na otpornost stanica na lijekove i njihovo podrijetlo, ukazuju na njihovu moguću upotrebu u dijagnostici, dok istovremeno povećanje citotoksičnosti fotoaktivacijom ukazuje na njihovo moguće korištenje u terapiji. Razlike u akumulaciji Cy7 boja s obzirom na vrstu stanica najvjerojatnije su uzrokovana različitim ekspresijama transportera OATP analiziran metodom Western blot . Preliminarni rezultati, dobiveni korištenjem testa sa sulforadaminom B, ukazuju na moguće djelovanje boja Cy7 na sintezu proteina.
Abstract (english) Heptamethine dyes from the group of cyanine dyes have fluorescent properties and work in the near-infrared region. Due to their low phototoxicity, they have a potential application for diagnostic purposes. Thanks to their photosensitivity, they can also be used as part of photodynamic therapy in the treatment of certain types of tumors. During the preparation of this thesis, the biological properties of three Cy7 dyes were investigated: SB-35, SB-53 and SB-55, newly synthesized phenanthridine derivatives with amino acid substituents (glycine, lysine) and a guanidinocarbonylpyrrole unit. The effect of Cy7 dyes on cell metabolism, as a measure of viability, their accumulation in the cell and phototoxicity was tested using cervical cancer cells (HeLa), alveolar adenocarcinoma (A549), melanoma (RPMI-7951) and normal fibroblasts. The possible selectivity of the compounds, considering cell drug resistance, was tested on four additional cell lines: high-grade serous ovarian cancer cells (parental MES-OV and carboplatin-resistant MES-OV CBP) and ovarian adenocarcinoma cells (parental SK-OV-3 and carboplatin resistant line SK-OV-3 CBP). Using the 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, it was determined that the weak cytotoxicity of Cy7 dyes, but also the selectivity considering the resistance of cells to drugs and their origin, indicate their possible use in diagnostics, while the simultaneous increase in cytotoxicity by photoactivation indicates their possible use in therapy. Differences in the accumulation of Cy7 dyes considering the type of cells are most likely caused by different expressions of the OATP transporter which was analyzed by the Western blot method. Preliminary results, obtained using the sulforadamine S assay, indicate a possible effect of Cy7 dyes on protein synthesis.
Keywords
heptametinske cijaninske boje
tumor
fotodinamična terapija
dijagnostika
Keywords (english)
heptamethine cyanine dyes
tumor
photodynamic therapy
diagnostics
Language croatian URN:NBN urn:nbn:hr:217:239601 Project Number: IP-2022-10-5202 Study programme Title: Experimental Biology-University graduate programme Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2024-07-29 12:01:40
