Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model.

Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparticles surfaces to exploit overexpression of folate receptors in tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive folate-coated DOX-loaded liposomes (SpHL-DOX-Fol) in a 4T1 breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher tumor uptake for radiolabeled SpHL-Fol (99mTc-SpHL-Fol) 4 h after intravenous administration was observed in comparision with non-folate-coated liposomes (99mTc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX tumor delivery and reduce dose-limiting toxicity.

Boron nitride nanotubes coated with organic hydrophilic agents: stability and cytocompatibility studies.

In the present study, Boron Nitride Nanotubes (BNNTs) were synthesized and functionalized with organic hydrophilic agents constituted by glucosamine (GA), polyethylene glycol (PEG)1000, and chitosan (CH) forming new singular systems. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy, while their surface charge was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by Transmission Electron Microscopy. The functionalization was evaluated by Thermogravimetry analysis and Fourier Transformer Infrared Spectroscopy. The results showed that BNNTs were successfully obtained and functionalized, reaching a mean size and dispersity deemed adequate for in vitro studies. The in vitro stability tests also revealed a good adhesion of functionalized agents on BNNT surfaces. Finally, the in vitro cytocompatibility of functionalized BNNTs against MCR-5 cells was evaluated, and the results revealed that none of the different functionalization agents disturbed the propagation of normal cells up to the concentration of 50 µg/mL. Furthermore, in this concentration, no significantly chromosomal or morphologic alterations or increase in ROS (Reactive Oxygen Species) could be observed. Thus, findings from the present study reveal an important stability and cytocompatibility of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures.

Boron nitride nanotubes radiolabeled with 99mTc: preparation, physicochemical characterization, biodistribution study, and scintigraphic imaging in Swiss mice.

In the present study, boron nitride nanotubes (BNNTs) were synthesized from an innovative process and functionalized with a glycol chitosan polymer in CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) laboratories. As a means of studying their in vivo biodistribution behavior, these nanotubes were radiolabeled with (99m)Tc and injected in mice. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy (PCS), while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by scanning electron microscopy (SEM). The functionalization in the nanotubes was evaluated by thermogravimetry analysis (TGA) and Fourier transformer infrared spectroscopy. The results showed that BNNTs were obtained and functionalized successfully, reaching a mean size and dispersity deemed adequate for in vivo studies. The BNNTs were also evaluated by ex vivo biodistribution studies and scintigraphic imaging in healthy mice. The results showed that nanostructures, after 24h, having accumulated in the liver, spleen and gut, and eliminated via renal excretion. The findings from this study reveal a potential application of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures.