Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

We determined the anticancer efficacy and internalization mechanism of our polymeric-ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts.

Effect of B4C, TiB2 and ZrSiO4 ceramic particles on mechanical properties of aluminium matrix composites: Experimental investigation and predictive modelling

This paper focuses on the influence of processing temperature and inclusion of micron-sized B4C, TiB2 and ZrSiO4 on the mechanical performance of aluminium matrix composites fabricated through stir casting. The ceramic/aluminium composite could withstand greater external loads, due to interfacial ceramic/aluminium bonding effect on the movement of grain and twin boundaries. Based on experimental results, the tensile strength and hardness of ceramic reinforced composite are significantly increased. The maximum improvement is achieved through adding ZrSiO4 and TiB2, which has led to 52% and 125% increase in tensile strength and hardness, respectively. To predict the effect of incorporating ceramic reinforcements on the mechanical properties of composites, experimental data of mechanical tests are used to create 3 models named Levenberg-Marquardt Algorithm (LMA) neural networks. The results show that the LMA- neural networks models have a high level of accuracy in the prediction of mechanical properties for ceramic reinforced-aluminium matrix composites.

Clouds for masses - toward ubiquitous and transparent clouds

Since the development of the computer, user orientated innovations such as graphical operating systems, mice, and mobile devices have made computing ubiquitous in modern society. The cloud is the next step in this process. Through the cloud, computing has undergone co modification and has been made available as a utility. However, in comparison to other commodities such as water and electricity, clouds (in particular IaaS and PaaS) have not reached the same penetration into the global market. We propose that through further abstraction, future clouds will be ubiquitous and transparent, made accessible to ordinary users and integrated into all aspects of society. This paper presents a concept and path to this ubiquitous and transparent cloud, accessible by the masses.