Search

Bismuth ferrite (BFO) harmonic nanoparticles (NPs) display high nonlinear optical efficiency and excellent biocompatibility profile which make them attractive for the development of diagnostic applications as contrast agents. In this study, we present a general method for the functionalization of this material with chemical ligands targeting cancer molecular biomarkers. In particular, a conjugation protocol based on click reaction between alkynyl-containing targeting ligands and poly(ethylene glycol)-coated BFO NPs (67.7nm) displaying surface reactive azido groups was developed. Copper-free click reaction allowed fast and efficient conjugation of a covalent inhibitor of prolyl-specific endopeptidases to coated BFO NPs. The ability of these functionalized nanomaterials (134.2nm) to act as imaging probes for cancer cells was demonstrated by the selective labeling of human lung cancer cells.

A route of accumulation and elimination of therapeutic engineered nanoparticles (NPs) may be the kidney. Therefore, the interactions of different solid-core inorganic NPs (titanium-, silica-, and iron oxide-based NPs) were studied in vitro with the MDCK and LLC-PK epithelial cells as representative cells of the renal epithelia. Following cell exposure to the NPs, observations include cytotoxicity for oleic acid-coated iron oxide NPs, the production of reactive oxygen species for titanium dioxide NPs, and cell depletion of thiols for uncoated iron oxide NPs, whereas for silica NPs an apparent rapid and short-lived increase of thiol levels in both cell lines was observed. Following cell exposure to metallic NPs, the expression of the tranferrin receptor/CD71 was decreased in both cells by iron oxide NPs, but only in MDCK cells by titanium dioxide NPs. The tight association, then subsequent release of NPs by MDCK and LLC-PK kidney epithelial cells, showed that following exposure to the NPs, only MDCK cells could release iron oxide NPs, whereas both cells released titanium dioxide NPs. No transfer of any solid-core NPs across the cell layers was observed

The primary goal of this study was to design a fluorescent E-selectin-targeted iodine-containing liposome for specific E-selectin imaging with the use of micro-CT. The secondary goal was to correlate the results of micro-CT imaging with other imaging techniques with cellular resolution, i.e., confocal and intravital microscopy. E-selectin-targeted liposomes were tested on endothelial cells in culture and in vivo in HT-29 tumor-bearing mice (n = 12). The liposomes contained iodine (as micro-CT contrast medium) and fluorophore (as optical contrast medium) for confocal and intravital microscopy. Optical imaging methods were used to confirm at the cellular level, the observations made with micro-CT. An ischemia-reperfusion model was used to trigger neovessel formation for intravital imaging. The E-selectin-targeted liposomes were avidly taken up by activated endothelial cells, whereas nontargeted liposomes were not. Direct binding of the E-selectin-targeted liposomes was proved by intravital microscopy, where bright spots clearly appeared on the activated vessels. Micro-CT imaging also demonstrated accumulation of the targeted lipsomes into subcutaneous tumor by an increase of 32 ± 8HU. Hence, internalization by activated endothelial cells was rapid and mediated by E-selectin. We conclude that micro-CT associated with specific molecular contrast agent is able to detect specific molecular markers on activated vessel walls in vivo

Purpose: Doxorubicin is a first-line chemotherapeutic for breast cancer; however, it is associated with severe side effects to non-tumoral tissues. Thus, it is necessary to develop new therapeutic combinations to improve doxorubicin effects at lower concentration of the drug associated with protective effects for non-tumoral cells. In this work, we evaluated whether the plant-derived flavonoid quercetin may represent such an agent. Methods: The effects of doxorubicin and quercetin as single agents and in combination were evaluated on cell survival, DNA and protein synthesis, oxidative stress, migratory potential and cytoskeleton and nucleus structure in highly invasive and poorly invasive human breast cancer cells in comparison with non-tumoral human breast cells. Results: In human breast cancer cells, quercetin potentiated antitumor effects of doxorubicin specifically in the highly invasive breast cancer cells and attenuated unwanted cytotoxicity to non-tumoral cells. Quercetin interfered with cell metabolism, GST activity, cytoskeleton and invasive properties specifically in breast tumor cells compared with non-tumoral breast cells. Doxorubicin induced DNA damage in tumor and non-tumor cells; however, quercetin reduced this damage only in non-tumoral cells, thus offering a protective effect for these cells. Quercetin also induced polynucleation in aggressive tumor cells, which was maintained in combination with doxorubicin. Conclusions: By combining quercetin with doxorubicin, an increase in doxorubicin effects was obtained specifically in the highly invasive breast cancer cells, while in non-tumoral cells quercetin reduced doxorubicin cytotoxic side effects. Thus, quercetin associated with doxorubicin demonstrated very promising properties for developing chemotherapeutics combinations for the therapy of breast cancer

Water-soluble metalla-cages were used to deliver hydrophobic porphin molecules to cancer cells. After internalization, the photosensitizer was photoactivated, significantly increasing the cytotoxicity in cells. During the transport, the photosensitizer remains nonreactive to light, offering a new strategy to tackle overall photosensitization, a limitation often encountered in photodynamic therapy.