Glycosylated conjugated oligomer and chlorophyll based nanoparticles for photodynamic therapy

Date
2023-01
Advisor
Tuncel, Dönüş
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Bilkent University
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Language
English
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Abstract

Nanomaterial-based therapeutic agents are drawing a lot of attention because numerous capabilities, including drugs, targeting groups, and photoactive units, can be combined on one platform to treat infectious diseases and cancer. In this regard, two different nanomaterials and their nanomedicine applications were re-ported. Firstly, red-emitting glycosylated conjugated oligomer (COL) nanopar-ticle was prepared and hybrid conjugation with gold nanoparticles was prepared by the nanoprecipitation method in order to examine photothermal applications. Due to their authentic electronic and optical characteristics, showing high sin-glet oxygen production ability, enabling control of the sizes of nanoparticles by acetyl groups in the side chains, enhancing their stability, and improving cell permeability via the hydrophobic effect they are promoting photosensitizers for photodynamic therapy. Secondly, chlorophyll, a natural photo absorbent, was ex-tracted from spinach leaves, and chlorophyll nanoparticles were prepared by nano-precipitation method because of their promoting properties which are high bio-compatibility, low production cost, and natural reductive chemical atmosphere, containing plenty of hydrogen atoms and being environmentally friendly. Then, hybrid conjugation with gold nanoparticles was prepared to investigate photother-mal therapy application. Both of the nanoparticles showed a high generation ability of reactive oxygen species (ROS) even at low light intensities and short exposure times which makes nanoparticles an ideal photosensitizer. From the antibacterial experiment, when Gram-negative (Escherichia coli, E. coli) bacteria were incubated with chlorophyll-based nanoparticles, a reduction up to 2.8-log and 2.33-log in colony-forming units (CFUs) was obtained under light irradiation for Chl-Au and Chl nanoparticles, respectively. Also, these nanoparticles showed minimal dark cytotoxicity (0.32-log and 0.15-log). On the other hand, conjugated oligomer-based nanoparticles precipitated in bacterial suspension and were un-able to pass across the cell wall of bacteria which was proved by SEM images and 4 mm and 5 mm inhibition zone were recorded for COL and COL-Au nanopar-ticles which are highly lower than ampicillin (7 mm). Along with these results, it is deduced that conjugated oligomer nanoparticles are not proper for antibac-terial photodynamic applications although the interaction between the bacterial cell wall and nanoparticle was promoted with gold conjugation. For anticancer photodynamic therapy applications, MCF-7 breast cancer cells were treated with these nanoparticles in the dark and under white light illumination for 20 min-utes, and the decline in cell viability was recorded at 50 %, 60 %, and 58 %, 72 %reduction for Chl, Chl-Au, and COL, Chl-Au nanoparticles, respectively. Also, they demonstrated dark cytotoxicity with the increment of concentration. Ad-ditionally, they also demonstrated the capacity for cellular imaging due to their inherent fluorescent properties, which might be used for image-guided PDT ap-plications. Along with this, the cytotoxicity results were supported by displaying the cellular uptake of nanoparticles and their surrounding the nucleus of breast cancer cells.

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Keywords
Photoactive conjugated oligomer, Chlorophyll, Photodynamic therapy, Singlet oxygen, Cancer treatment, Antibacterial applications
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Published Version (Please cite this version)