Bio-Functionalization of SWCNTs with Combretastatin A4 for Targeted Cancer Therapy
| dc.contributor.advisor | العسالي, محي الدين | |
| dc.contributor.author | حمد, ديمه فهيم محمد رشدي | |
| dc.date.accessioned | 2018-09-26T08:34:17Z | |
| dc.date.available | 2018-09-26T08:34:17Z | |
| dc.date.issued | 2017-05-25 | |
| dc.description.abstract | Chemotherapy is a mainstay approach in the management of cancer. Unfortunately, it can affect not only the cancerous cells but also the healthy ones resulting in a number of severe side effects. Therefore, many researchers are keen to developing new Drug Delivery Systems (DDS) that may in one hand help reducing the used doses and on the other hand target the delivery of the chemotherapy to cancer cells. Some modern investigational DDS in this field are based on carbon nanotubes (CNTs) technology. The aim of this work is to covalently functionalize single walled carbon nanotubes (SWCNTs) with Combretastatin A4 (CA4) through click reaction in the presence of tetraethylene glycol linker to improve the solubility and dispersibility of the developed nano-drug. Moreover, in order to specifically target the cancer cells, a targeting agent folic acid was also loaded on the nano-system. The characterization of the developed nano-drug by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed good dispersibility of the functionalized SWCNTs with diameters of (5-15) nm. Moreover, the efficiency of functionalization was determined by thermogravometric analysis (TGA) showing 45% of functionalization in the case of CA4-SWCNTs (7) and 50% for CA4-FA-SWCNTs (13). The in vitro release profile of CA4 showed that approximately 90% of the loaded drug was released over 50 hrs at pH 7.4 and 37 ºC. MTS proliferation test was implemented to determine the suitable concentration for the CA4-SWCNTs (7), which was found to be 15 ng/ml. After that the cytotoxic activity of the nano-drug was evaluated by flow cytometry using Annexin V/Propidium iodide (PI) test. In comparison with free CA4, CA4-SWCNTs (7) treatment demonstrated a significant increase in necrotic cells (around 50%) at the expense of the proportion of the apoptotic cells. Moreover, cell cycle PI test demonstrated that free CA4 and CA4-SWCNTs (7) caused G2/M arrest. However with CA4 treatment higher proportion of cells were in the S-phase while with CA4-SWCNTs treatment greater proportion of cells appeared to be in the G1-phase. Taken together, the provided data suggest that the novel CA4-SWCNTs (7) has a significant anticancer activity that might be superior to that of free CA4. The anticancer activity of CA4-FA-SWCNTs (13) is under investigation. | en_US |
| dc.identifier.uri | https://hdl.handle.net/20.500.11888/13948 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | An-Najah National University | en_US |
| dc.title | Bio-Functionalization of SWCNTs with Combretastatin A4 for Targeted Cancer Therapy | en_US |
| dc.title.alternative | التفعيل البيولوجي لأنابيب الكربون النانونية بمركب كومبريتاستاتين أ4 لعلاج السرطان بطريقة مستهدفة | en_US |
| dc.type | Thesis | en_US |