Development and Characterization of PEG-B-PCL Micelles Carrying Anticancer Agents

Download

Ph.D. Thesis - Gülhan Işık.pdf

Date

2022-2-9

Author

Işık, Gülhan

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

263
views

101
downloads

Cancer is a disease that decreases the quality of life. Many cancer drugs are either toxic or not effective due to their fast removal by reticuloendothelial system. Therefore, nano-sized drug delivery systems, especially the ones carrying the drugs directly to tumor, gained attention in the last decades. The aim of the study was to prepare nano-sized drug carrying micelles (drug conjugated and drug loaded) from methoxy polyethylene glycol-block-polycaprolactone (mPEG-b-PCL). In order to conjugate drugs, mPEG-b-PCL was activated with hydrazide groups. Doxorubicin (DOX) was conjugated covalently (at 60ºC), and lithocholic acid (LCA) was conjugated ionically (at 60ºC and 25ºC) to obtain micelles (coded as DOXconj-M, LCA60**M and LCA25**M, respectively). Micelles having no conjugation, but loading of DOX (DOXld-M), and micelles having both drugs together (DL-M) were also prepared. Micelles demonstrated faster drug release in acidic media than the neutral media, which is advantageous for the treatment of cancer since cancer tissue is more acidic than the healthy tissue. Cell culture studies show that micelles having no drugs are not cytotoxic. Internalization of the micelles into MDA-MB-231 cancer cells was determined by using coumarin-6 loaded micelles for LCA containing micelles (LCA60**M and LCA25**M) and DOX for DOX containing micelles (DOXconj-M, DOXld-M, and DL-M). All micelles displayed low cell migration and high anti-proliferative effect on MDA-MB-231 cells. Moreover, the ones having LCA (LCA60**M, LCA25**M and DL-M) led a decrease in lipogenic activity, but DOXconj-M and DOXld-M did not change lipid droplet formation. An increase in the number of apoptotic cells, as well as in apoptotic genes of Bax and p53 expressions, and a significant decrease in anti-apoptotic genes of Bcl-2 and Bcl-xL expressions were observed after the treatment of the cells with DOXld-M and DL-M. All micelles prepared in this study caused a decrease in the mitochondrial transmembrane potential of the cells, which results in apoptosis, and an increase in ROS generation, which was significantly higher in the cells treated with DOXconj-M, DOXld-M, and DL-M compared to free DOX applied ones. Micelles having LCA caused a significant decrease in angiogenesis ability of HUVECs. In the future these types of micelles especially immunomicelles targeted to cancer cells will be the candidate carriers in cancer therapy.

Subject Keywords

Lithocholic acid, Doxorubicin, pH sensitive, PEG-b-PCL micelles, MDA-MB-231 cells

URI

https://hdl.handle.net/11511/96702

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines Hawash, Mohammed; Kahraman, Deniz Cansen; Ergun, Sezen Guntekin; Cetin-Atalay, Rengul; BAYTAŞ, SULTAN (2021-12-01) Background Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, H-1-NMR and C-13-NMR spectroscopy and element analysis. Results The cytotoxic activity was performed against Huh7, MCF7 and HCT116...
Investigation of Effects of Microenvironment and Immune Cells onTumor Growth by Agent Based Modeling Orta Doğu Teknik Üniversitesi, Deniz Bilimleri Enstitüsü (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10) Cancer is one of the diseases that humanity suffered for a long time. We understand many aspects of this disease, but there is still much to learn. Because it is a complex disease that affects many processes, organs, cell types, and so on. We need to investigate cellular components, interactions and processes that are related to cancer as a whole to understand its structure. In this scope, investigating the microenvironment of tumors and interactions in it can reveal fundamental features of cancer. One of t...
Contribution of different types of -omic data on personalized diagnosis of cancer Tanıl, Ezgi; Kızılilsoley, Nehir; Nikerel, Emrah (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10) Cancer is a complex disease which is one of the main causes of death globally. Survival rate of cancer increases if early diagnosis and application of appropriate treatment are available [1,2]. Understanding differential response from one patient to another can aid in drug targeting, understanding disease progression and finding efficient treatment strategies. Tumour cells shown to have altered metabolism and the most commonly defined example is the Warburg effect in which tumour cells shown to use lactic a...
Investigaton of chemopreventive properties of Urtica Dioica L., in MCF-7 and MDA231 breast cancer cell lines Güler, Elif; İşcan, Mesude; Department of Biology (2011) Cancer is a major health problem in developing world with mostly unsufficient treatment. Cancer prevention through dietary modification appears to be a practical and cost effective possibility. The aim of present study is to investigate the chemical components of “Urtica diocia,L (U. diocia) grown in Turkey” and the possible protective potential of its aqueous extract against breast cancer cell lines. U. diocia was extracted by maceration method which was performed for 6,12, 24, and 36 hours, at 50°C, 37°C,...
Characterization of liposomal celecoxib formulation as a drug delivery system in colorectal cancer cell lines Erdoğ, Aslı; Banerjee, Sreeparna; Department of Biotechnology (2012) Colorectal carcinoma (CRC) is one of the most common cancers and is the leading cause of cancer deaths in much of the developed world. Owing to the high incidence of drug resistance and potential toxic effects of chemotherapy drugs, much research is currently underway to design better strategies for smart drug delivery systems. Cyclooxygenase-2 (COX-2) pathway is associated with poor prognosis in colon carcinomas. The selective COX-2 inhibitor drug Celecoxib (CLX) has been shown to posses COX-2 independent ...

Citation Formats

G. Işık, “Development and Characterization of PEG-B-PCL Micelles Carrying Anticancer Agents,” Ph.D. - Doctoral Program, Middle East Technical University, 2022.