▎ 摘　　要

As a fascinating alternative to overcome the undesired side effects and to improve therapeutic efficacy and water solubility of chemotherapeutic agent tamoxifen (TAM), the simplistic method based on folic acid (FA) tagged amphiphilic graphene oxide (GO) for cell specific delivery was adopted. Besides, FA-GO also served as template for synthesis of Ag NP. Hence, the present study demonstrates a co-delivery system for folate receptor (FR) targeted delivery of anticancer agents TAM and Ag NP for combination therapeutics of breast cancer in vitro. The method involved the syntheses of sulfonate modified GO with FA functionalization which was validated by FTIR and UV-vis analysis. TAM was loaded onto the FA-GO nanocarrier by physiosorption of hydrophobic drug onto surface with encapsulation efficiency (EE) around 98%. The synthesized FAGO@ AgNP@TAMnanocarrier was physiologically stable with average zeta potential and hydrodynamic size of -40 mV, 167 nm contrarily to alone GO with -29.5 mV, 5 nm respectively. Cellular uptake studies revealed specificity of nanocarrier towards FR (+ ve) breast carcinoma (MCF-7 cell line) compared to FR (-ve) lung carcinoma (A549 cell line). Based on cell specificity of nanocarrier, the cytotoxicity of various nanocarrier combinations was investigated towards MCF-7 cells. The combination exhibited superior cytotoxic effect than TAM, Ag NP alone at relatively lower concentrations with notable cell cycle growth arrest in sub-G1 phase. The FA-GO@AgNP@TAMnanocarrier showed elevated intracellular reactive oxygen species (ROS) generation with considerable dissipation of mitochondrial membrane potential (MMP). Furthermore the semi-quantitative RT-PCR analysis showed increased pro-apoptotic genes expression with highest expression of caspase-3. Altogether the study suggests mitochondria mediated apoptotic signaling pathway. These findings suggest the above designed nanocarrier could serve as the potential candidate for targeted combination breast cancer therapy.