Ovarian cancer is a common cause of cancer death in women and is associated with the highest mortality rates of all gynecological malignancies. Carboplatin (CBP) is the most used cytotoxic agent in the treatment of ovarian cancer. Herein, we design and assess a CBP nanotherapeutic delivery system which allows combinatorial functionalities of chemotherapy, pH sensing, and multimodal traceable properties inside live NIH:OVCAR-3 ovarian cancer cells. In our design, a pH-sensitive Raman reporter, 4-mercaptobenzoic acid (4MBA) is anchored onto the surface of chitosan-coated silver nanotriangles (chit-AgNTs) to generate a robust surface-enhanced Raman scattering (SERS) traceable system. To endow this nanoplatform with chemotherapeutic abilities, CBP is then loaded to 4MBA-labeled chit-AgNTs (4MBA-chit-AgNTs) core under alkaline conditions. The uptake and tracking potential of CBP-4MBA-chit-AgNTs at different Z-depths inside live ovarian cancer cells is evaluated by dark-field and differential interference contrast (DIC) microscopy. The ability of CBP-4MBA-chit-AgNTs to operate as near-infrared (NIR)-responsive contrast agents is validated using two noninvasive techniques: two-photon (TP)-excited fluorescence lifetime imaging microscopy (FLIM) and confocal Raman microscopy (CRM). The most informative data about the precise localization of nanocarriers inside cells correlated with intracellular pH sensing is provided by multivariate analysis of Raman spectra collected by scanning CRM. The in vitro cell proliferation assay clearly shows the effectiveness of the prepared nanocarriers in inhibiting the growth of NIH:OVCAR-3 cancer cells. We anticipate that this class of nanocarriers holds great promise for application in image-guided ovarian cancer chemotherapy.
Gold nanoparticles (GNPs) were obtained by green synthesis with an extract fromCornus masfruits (GNPs-CM), characterized by several methods, and their biologic effects were evaluated on two cell lines: HaCaT, normal keratinocytes, and A431, epidermoid carcinoma. GNPs were spherical with sizes between 2 and 24 nm. Their optical spectra had a dominant plasmonic band centered at 525 nm; zeta potential distribution was narrow, centered at −19.7 mV, and the mean hydrodynamic diameter was 58 nm. GNPs were visualized in both cell types entering the cells by endocytosis. The amount of gold uptaken by the cells was dose and time dependent. The intracellular concentration of Au ions was higher in HaCaT compared to A431 cells. The toxicity of GNPs-CM was dose dependent being significant only when the highest concentrations were employed. A431 cells were less affected compared to HaCaT cells, but the difference was not statistically significant. ROS production was not significant, except in HaCaT cells at the highest concentration. The comet assay revealed no significant supplementary DNA lesions, while the secretion of inflammatory cytokines was modulated by the presence of GNPs only when the cells were additionally irradiated with UVB. These results recommend GNPs-CM for further testing and possible dermatological applications.
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