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ARTICLE This journal isMesoporous strontium hydroxyapatite (SrHAp) nanorods (NRs) have been successfully synthesized using a simple and efficient chemical route, i.e. the hydrothermal method. A structural and morphological characterization of the as synthesized SrHAp NRs has been performed by transmission electron microscopy (TEM) and high angle annular dark field scanning transmission electron microscopy (HAADF-STEM). TEM and HAADF-STEM measurements of the NRs reveal the coexistence of longer and shorter particles with a length ranging from 50nm to 400nm and a diameter of about 20-40nm. Electron tomography measurements of the NRs allow us to better visualize the mesopores and their facets. Two model drugs, Risperdone as hydrophobic and Pramipexole as hydrophilic, were loaded into the SrHAp NRs. These nanorods were coated using a modified chitosan (CS) with poly(2-hydroxyethyl methacrylate) (PHEMA), in order to encapsulate the drug-loaded SrHAp nanoparticles and to reduce the cytotoxicity of the loaded materials. The drug release from neat and encapsulated SrHAp NRs mainly depends on the drug hydrophilicity. Importantly, although neat SrHAp nanorods exhibit some cytotoxicity against Caco-2 cells, the Cs-g-PHEMA-SrHAp drug-loaded nanorods show an acceptable cytocompatibility.

PURPOSE: Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented. METHODS:The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFR pos , EGFR neg ) cultures. Moreover, the molecular mechanism of action underlying their pharmacological response is also analyzed. RESULTS:The pharmacological anticancer profile of DLC-functionalized carboranes is characterized by: a) a marked in vitro selectivity, due to lower concentration range needed (ca. 10 fold) to exert their cell growth-arrest effect on U-87 MG and HSC-3, as compared with that on MRC-5, Vero; b) a similar selective growth inhibition behavior towards EGFR pos and EGFR neg cultures (>10 fold difference in potency) without, however, the activation of apoptosis in cultures; c) notably, in marked contrast to cancer cells, normal cells are capable of recapitulating their full proliferation potential following exposure to DLC-carboranes; and, d) such pharmacological effects of DLC-carboranes has been unveiled to be elicited at the molecular level through activation of the p53/p21 axis. CONCLUSIONS:Overall, the data presented in this work indicates the potential of the DLC-functionalized carboranes to act as new selective anticancer therapeutics that 3 may be used autonomously or in therapies involving radiation with thermal neutrons.Importantly, such bifunctional capacity may be beneficial in cancer therapy.

The observed alterations of their expression suggest a role of Dsg3 and γ-catenin (additionally to E-cadherin/β-catenin) as biomarkers of malignant transformation risk of oral dysplasia and the biological behavior (aggressiveness) of oral cancer, respectively.

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