Design and synthesis of cisplatin-loaded multifunctional nanocarriers and evaluation of their anticancer activity against afatinib-resistant triple-negative breast cancer (TNBC) cells

In this thesis the synthesis of multifunctional nanocarrier as a drug delivery material was carried out. The aim of the study was to apply these designed nanocarrier as targeted delivery carriers in triple negative breast cancer. These nanocarriers were synthesized and characterized by using infrared spectroscopy (IR), ultraviolet-visible (UV-Vis), Nuclear magnetic resonance (NMR) and mass spectroscopy (MS), Differential scanning, thermogravimetry, Zeta Sizer (DLS), and fluorescence spectrometry. The results of analysis showed that core molecule BHX (40,30,20) of nanomaterial was successfully functionalized with HFBCE and Flamma 774 isothiocyanate. As well as shell of hyaluronic acid with folic acid and -R8-c(RGD) peptide. Zeta sizer analysis showed that particles are less than 200 nm which was further confirmed by SEM and TEM analysis. Thermogravimetric analysis supports the functionalization of both BHX and HA, which was further confirmed by NMR, and MALDI-TOF analysis. Cytotoxicity analysis of these nanomaterials showed no toxic effect to both normal CC14CO and cancerous cell lines CAL-51. Fluorescence spectrometric results of these nanosized multifunctional nanocarrier loaded with cisplatin, had shown successful uptake by cancerous cells. It was observed that cisplatin loaded nanocarriers significantly affect the cancerous cells compare to normal cell line which shows targeting enhance the uptake of nanocarriers in cancer cells compare to normal cell line. Similar results were observed in free cisplatin and loaded onto nanocarriers. Anticancer activity of nanocarriers loaded with cisplatin were more affective compared to free cisplatin in afatinib resistant CAL-51 cells