Enhanced Intracellular Ca2+ Nanogenerator for Tumor-Specific Synergistic Therapy via Disruption of Mitochondrial Ca2+ Homeostasis and Photothermal Therapy.

Breast cancer therapy has always been a hard but urgent issue. Disruption of mitochondrial Ca2+ homeostasis has been reported as an effective antitumor strategy, while how to contribute to mitochondrial Ca2+ overload effectively is a critical issue. To solve this issue, we designed and engineered a dual enhanced Ca2+ nanogenerator (DECaNG), which can induce elevation of intracellular Ca2+ through the following three ways: Calcium phosphate (CaP)-doped hollow mesoporous copper sulfide was the basic Ca2+ nanogenerator to generate Ca2+ directly and persistently in the lysosomes (low pH). Near-infrared light radiation (NIR, such as 808 nm laser) can accelerate Ca2+ generation from the basic Ca2+ nanogenerator by disturbing the crystal lattice of hollow mesoporous copper sulfide via NIR-induced heat. Curcumin can facilitate Ca2+ release from the endoplasmic reticulum to cytoplasm and inhibit expelling of Ca2+ in cytoplasm through the cytoplasmic membrane. The in vitro study showed that DECaNG could produce a large amount of Ca2+ directly and persistently to flow to mitochondria, leading to upregulation of Caspase-3, cytochrome c, and downregulation of Bcl-2 and ATP followed by cell apoptosis. In addition, DECaNG had an outstanding photothermal effect. Interestingly, it was found that DECaNG exerted a stronger photothermal effect at lower pH due to the super small nanoparticles effect, thus enhancing photothermal therapy. In the in vivo study, the nanoplatform had good tumor targeting and treatment efficacy via a combination of disruption of mitochondrial Ca2+ homeostasis and photothermal therapy. The metabolism of CaNG was sped up through disintegration of CaNG into smaller nanoparticles, reducing the retention time of the nanoplatform in vivo. Therefore, DECaNG can be a promising drug delivery system for breast cancer therapy.

[Comparison of Heavy Metal Contamination Characteristics in Surface Water in Different Functional Areas: A Case Study of Ningbo].

From industrial and commercial areas of Ningbo City, China, 85 surface water samples were collected. The concentrations of six heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) in the samples were measured, and the characteristics of the spatial distributions of those metals were analyzed. Through a combination of regional characteristics and Pearson correlation coefficients of the different heavy metals, the main pollution sources of the two areas were analyzed. The potential ecological risks of these heavy metals were evaluated by considering health risk and cancer risk indices. The results indicate that the heavy metal pollution of surface waters was serious in both the industrial and commercial areas. Furthermore, the differences between the two areas were also observed. In the industrial area, the average concentrations of the six heavy metals were, from highest to lowest, in the order: Zn >>Ni>Pb> Cr> Cu> Cd, and the main sources were industrial emissions. Four heavy metal concentrations exceeded the national environmental standard, which, from highest to lowest, were in the order: Cd> Pb> Cr >>Zn. In the commercial area, the average concentrations, from highest to lowest, were in the order: Cr> Pb >>Zn> Ni> Cd> Cu, and the main sources were road pollutants. Three heavy metal concentrations exceeded the national standard, and the order, from highest to lowest, was Cd> Pb>>Cr, with Cd and Pb having the most potential health risk. In both the industrial and commercial areas, there were some potential health risks and high carcinogenic risks. Cd, Cr, and Pb have the highest potential health risks, whereas Cr is the major potentially carcinogenic metal. The commercial area had 1.7 times the potential carcinogenic risk as that of the industrial area. The government should pay more attention to heavy metal pollution of surface waters in Ningbo City, China.