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The major challenge of curcumin (CUR) therapy is the low bioavailability in the tumor cells, which could be solved by targeting and manipulating nanoparticles (NPs) in the drug delivery systems (DDS) through enhancement of CUR uptake. In our study, ligand-targeted micelle NPs including BTN-poly ethylene glycol-polycaprolactone(PCL) (BTNcment-PEG-PCL) and mono methoxy poly (ethylene glycol)-poly (caprolactone) (mPEG-PCL) diblock co-polymers series were synthesized by way of a single-step nano-precipitation method and characterized by H NMR, FT-IR, DSC, DLS, TEM, and GPC techniques. Following CUR-loading on the NP series, cytotoxicity and cellular uptake of CUR-BTN-PEG-PCL and CUR-mPEG-PCL on human breast adenocarcinoma (MCF-7), Human embryonic kidney (HEK293), and human umbilical vein endothelial (HUVEC) cell lines were evaluated by MTT assay and microscope fluorescence, respectively. Then, in vitrostudies of targeted and untargeted NPs for the cell cycle and apoptosis assessment using flow cytometry have shown that CUR in CUR-BTN-PEG-PCL as a novel and targeted nanocarrier increases the cell population of Sub G1 and apoptosis. Moreover, in Ovochick chorioallantoic membrane (CAM) assay demonstrated that CUR-BTN-PEG-PCL has notably decreased tumor cell proliferation and angiogenesis due to enhanced CUR bioavailability for the site-specific tumor. In conclusion, BTN-PEG–PCL NPs as a novel and efficiently targeted nanocarrier predominantly improved CUR potential for cancer therapy.

In this project, in vitroand in vivoproperties of drug loaded nanocarriers based on miktoarm star copolymer mPEG-Lys-PCL2were evaluated. Miktoarm was synthesized using ring opening polymerization reaction. Then, quercetin which is a hydrophobic plant based flavonol, was loaded into star NCs using nanoprecipitation method. The structure and biocompatibility nanocarriers were determined using proton nuclear magnetic resonance, Fourier-transform infrared spectroscopy, dynamic light scattering, hemolysis assay and lethal dose test. According to biocompatibility tests, prepared nanocarrier was practically nontoxic. The drug loading and encapsulation efficiency of nanocarriers were high because of miktoarm has two hydrophobic arms and more spaces between layers in comparison with linear copolymer with the same material. The results of MTT assay proved that quercetin-loaded star nanocarriers possess acceptable toxicity on cancerous cells which is because of the ability of miktoarm to mimic phospholipid structure. Furthermore, in vivoresults showed the quercetin-loaded star nanocarriers is more effective to inhibit tumor volume than the free Quer. Also, the survival rate of mice treated with quercetin loaded star nanocarriers enhanced so that all the treated mice survived more than 75 days, and 20% of them were alive even after 85 days of experiment.

The present study aimed to synthesize AgFeO2 nanocarriers by a thermal treatment method and to test them with respect to their applicability in photodynamic therapy and drug delivery of anti-cancer drugs. Chemical structure, surface morphology, and magnetic properties of AgFeO2 were studied by X-ray diffractometer, Field emission-scanning electron microscopy, Fourier-transform infrared spectroscopy, and vibrating-sample magnetometer. The X-ray data for AgFeO2indicated the typical patterns of rhombohedral phase with delafossite structure. The biocompatibility of AgFeO2 was evaluated by a hemolysis test and a lethal dose test. The results confirmed the non-toxicity of the nanoparticles when used in photodynamic therapy. The loading and encapsulation efficiency of AgFeO2were 20.23 ± 0.24 and 84.55 ± 1.24, respectively. Furthermore, when the pH of the release media decreased from 7.4 to 5.8, the release rate of the Quercetin from Quercetin loaded AgFeO2increased from 52 to 70%. In the photodynamic therapy, the cytotoxicity of Quercetin, AgFeO2and Quercetin-loaded AgFeO2on tumor cells was studied. Cytotoxity of tumor cells treated with AgFeO2and Quercetin loaded AgFeO2under UV light significantly decreased from 65.7 to 27.2% to 23.58, and 7.6%, respectively. The results suggest that AgFeO2is a suitable nanocarrier to be used in drug delivery and photodynamic therapy.

In this project FA-L-PEG-PCL (FA: Folic acid, L: Lysine, PEG: Polyethylene glycol, PCL: Polycaprolactone) polymeric nanocarriers (NCs) were synthesized. In aqueous medium, this polymeric NCs could be self-assembled to form Round-shaped folate-functionalized micelles for delivery of Tamoxifen (TMX) and Quercetin (QUER) to cancerous cells. For determining the structure of this copolymer, fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and zeta sizer were used. The cytotoxicity of NCs was determined by hemolysis assay and this test displayed that the cytotoxicity of NCs is lower than 3%. To determine anticancer activity of synthesized drug loaded nanocarriers in vitrocell cytotoxicity analysis were performed on 4T1 cell line and in vivotreatment of tumors. Beside, histopathological study was performed to investigate the effect of drug loaded NCs on mice tissues. In vitroMTT experiment showed that QUER has significant synergistic effect for decreasing viability of the cancerous cell line (4T1); moreover, as an in vivotreatment of tumors, the FA-L-PEG-PCL-TMX-QUER exhibited a clear tumor-inhibiting effect; therefore, according to this results, we can conclude that The FA-L-PEG-PCL-TMX-QUER NCs had a considerable potential for oral delivery of combination drugs having most clinical application.