We investigated the anticancer potential of Ag-doped (0.5–5%) anatase TiO₂ NPs. Characterization study showed that dopant Ag was well-distributed on the surface of host TiO₂ NPs. Size (15 nm to 9 nm) and band gap energy (3.32 eV to 3.15 eV) of TiO₂ NPs were decreases with increasing the concentration of Ag dopant. Biological studies demonstrated that Ag-doped TiO₂ NP-induced cytotoxicity and apoptosis in human liver cancer (HepG2) cells. The toxic intensity of TiO₂ NPs was increases with increasing the amount of Ag-doping. The Ag-doped TiO₂ NPs further found to provoke reactive oxygen species (ROS) generation and antioxidants depletion. Toxicity induced by Ag-doped TiO₂ NPs in HepG2 cells was efficiently abrogated by antioxidant N-acetyl-cysteine (ROS scavenger). We also found that Ag-doped TiO₂ NPs induced cytotoxicity and oxidative stress in human lung (A549) and breast (MCF-7) cancer cells. Interestingly, Ag-doped TiO₂ NPs did not cause much toxicity to normal cells such as primary rat hepatocytes and human lung fibroblasts. Overall, we found that Ag-doped TiO₂ NPs have potential to selectively kill cancer cells while sparing normal cells. This study warranted further research on anticancer potential of Ag-doped TiO₂ NPs in various types of cancer cells and in vivo models.

We investigated whether Aluminum (Al) doping tunes band gap energy level as well as selective cytotoxicity of ZnO nanoparticles in human breast cancer cells (MCF-7). Pure and Al-doped ZnO nanoparticles were prepared by a simple sol-gel method. Characterization study confirmed the formation of single phase of Al_xZn_1-xO nanocrystals with the size range of 33–55 nm. Al-doping increased the band gap energy of ZnO nanoparticles (from 3.51 eV for pure to 3.87 eV for Al-doped ZnO). Al-doping also enhanced the cytotoxicity and oxidative stress response of ZnO nanoparticles in MCF-7 cells. The IC50 for undoped ZnO nanoparticles was 44 μg/ml while for the Al-doped ZnO counterparts was 31 μg/ml. Up-regulation of apoptotic genes (e.g. p53, bax/bcl2 ratio, caspase-3 & caspase-9) along with loss of mitochondrial membrane potential suggested that Al-doped ZnO nanoparticles induced apoptosis in MCF-7 cells through mitochondrial pathway. Importantly, Al-doping did not change the benign nature of ZnO nanoparticles towards normal cells suggesting that Al-doping improves the selective cytotoxicity of ZnO nanoparticles toward MCF-7 cells without affecting the normal cells. Our results indicated a novel approach through which the inherent selective cytotoxicity of ZnO nanoparticles against cancer cells can be further improved.

Surface-coated nanocarriers have been extensively used to enhance the delivery of anticancer drugs and improve their therapeutic index. In this study, chitosan (CS)-coated flexible liposomes (chitosomes) containing 5-fluorouracil (5-FU) were designed and characterized for use as a novel approach to target colon cancer cells. 5-FU-loaded flexible liposomes (F1, F2, and F3) and 5-FU-loaded chitosomes (F4, F5, and F6) were prepared using film hydration and electrostatic deposition techniques, respectively. The particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), morphology, and in vitro drug release ability, and cytotoxicity of the formulations were determined. The results revealed that the size of chitosomes ranged from 212 to 271 nm with a positive surface charge of 6.1 to 14.7 mV, whereas the particle size of liposomes ranged from 108 to 234 nm with negative surface charges of -2.3 to -16.3. F3 and F6 had a spherical shape with a rough surface structure. The in vitro drug release study revealed that chitosomes retard 5-FU release as opposed to the 5-FU solution and liposomes. The cytotoxicity study using a colon cancer cell line (HT-29) showed that 5-FU-loaded chitosomes were more effective in killing cancer cells in a sustained manner than liposomes and the 5-FU solution. Chitosomes were therefore successfully developed as nanocarriers of 5-FU, with potential cytotoxicity for colorectal cancer cells.