Studies on Iron(III) Complexes for Cellular Imaging and Targeted Photodynamic Therapy (Record no. 431563)
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| 000 -LEADER | |
|---|---|
| fixed length control field | 04437nam a22002177a 4500 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 240319b |||||||| |||| 00| 0 eng d |
| 082 ## - DEWEY DECIMAL CLASSIFICATION NUMBER | |
| Classification number | 546 |
| Item number | SAH |
| 100 ## - MAIN ENTRY--PERSONAL NAME | |
| Personal name | Sahoo, Somarupa |
| 245 ## - TITLE STATEMENT | |
| Title | Studies on Iron(III) Complexes for Cellular Imaging and Targeted Photodynamic Therapy |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT) | |
| Place of publication, distribution, etc | Bangalore: |
| Name of publisher, distributor, etc | Indian Institute of Science, |
| Date of publication, distribution, etc | 2023. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | xii, 366p.: |
| Other physical details | col. ill. |
| Accompanying material | e-Thesis |
| Size of unit | 18.87Mb |
| 502 ## - DISSERTATION NOTE | |
| Dissertation note | PhD;2023;Inorganic and Physical Chemistry |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc | Cancer is caused by uncontrolled division of abnormal cells. Surgery, chemotherapy, and radiation therapy are most widely used for its treatment. However, due to serious limitations of these traditional treatment modalities, Photodynamic Therapy (PDT) is currently being explored as an adjuvant/mainstream alternative. PDT is a medical technique that utilizes light, molecular oxygen (3O2) and a photosensitizer (PS) to generate cytotoxic reactive oxygen species (ROS) with spatio-temporal control, resulting in a specificity of drug action. Currently, clinical PDT is dominated by tetrapyrrolic PSs such as Photofrin® that require a high dose for a therapeutic effect, often resulting in skin sensitivity and hepatotoxicity. The systemic toxicity and acquired drug resistance linked with exogenous heavy metal chemotherapeutics like cisplatin have propelled research towards the development of biocompatible transition metal-based anticancer agents. In this regard, the primary objective of this thesis is to investigate the cytotoxic potential of Fe(III) complexes bound to different PSs that can be activated upon irradiation with visible or red light. In order to enhance the anticancer efficacy of the naturally occurring drug “curcumin”, two iron(III) complexes of curcumin were synthesized, conjugated to a tridentate biotin (Vitamin H) molecule as an ancillary ligand.[1] Binding to iron(III) provided stability to curcumin from hydrolytic degradation under physiological conditions. Due to the presence of cancer targeting biotin, an enhanced cellular uptake and cancer cell selective PDT effect was observed in HeLa (cervical) and MCF-7 (breast) cell lines, along with a 5-fold enhancement in cytotoxicity in HepG2 (liver) cancer cells. Further, a series of iron(III) complexes containing vitamin B6 Schiff base and a robust PS known as BODIPY (boron-dipyrromethene) were designed and studied for their targeted PDT effect.[2] The green fluorescent complex displayed in-vitro fluorescence at very low concentrations indicating a lysosomal localization. The diiodo-BODIPY containing complex effectively generated singlet oxygen (1O2) as the ROS ( > 0.6) upon irradiation with visible light of 400-700 nm. This was followed by the synthesis, characterization and study of two iron(III) complexes containing glycosylated benzyl-dipicolylamine with a BODIPY-tagged catecholate unit.[3] The complexes showed intense absorption bands with apoptotic PDT activity upon red-light irradiation (600−720 nm). Activation of PSs within the “PDT window” of 600-850 nm is of significance, as red light can penetrate deeper into the body tissues. The complexes were photocytotoxic towards a variety of cancer cells at sub-micromolar concentrations, with a photocytotoxicity index of >1200. The complexes were highly photostable in biological medium and remained non-toxic in dark conditions. Apart from monolayers, drug accumulation and fluorescence was also studied inside 3D tumour spheroids. Finally, we synthesized and studied two new iron(III) complexes containing a tridentate BODIPY ligand and its dibrominated analogue as photosensitizers, conjugated to esculetin–an O,O-donor coumarin ligand with its own anti-neoplastic properties.[4] These complexes generated both hydroxyl radicals (OH•) and singlet oxygen via dual type-I/II photosensitization pathways and exerted PDT effect upon red light activation. In summary, through this thesis, we present the systematic development of several series of new iron(III) complexes with photochemotherapeutic and cellular imaging properties, highlighting their immense potential as targeted PDT metallodrugs in cancer treatment. |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name as entry element | Photodynamic Therapy |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name as entry element | Photochemotherapeutic |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name as entry element | Iron complex |
| 700 ## - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Advised by Chakravarthy, Akhil R |
| 700 ## - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Advised by Thilagar, Pakkirisamy |
| 856 ## - ELECTRONIC LOCATION AND ACCESS | |
| Uniform Resource Identifier | https://etd.iisc.ac.in/handle/2005/6441 |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Koha item type | Thesis |
No items available.
