Arsenic sulfide (As
4
S
4
) is a mineral drug that can be administrated orally and has been applied in the treatment of myeloid leukemia. The aim of this work is to investigate the therapeutic effect of As
4
S
4
in highly metastatic triple-negative breast cancer (TNBC) animal model, as As
4
S
4
has not been applied in the treatment of breast cancer yet. To overcome the poor solubility of original As
4
S
4
, a formulation of hydrophilic As
4
S
4
nanoparticles (e-As
4
S
4
) developed previously was applied to mouse breast cancer cells as well as the tumor-bearing mice. It was shown that e-As
4
S
4
was much more cytotoxic than r-As
4
S
4
, strongly inhibiting the proliferation of the cells and scavenging intracellular reactive oxygen species (ROS). The oral administration of e-As
4
S
4
significantly increased the accumulation of arsenic in the tumor tissue and eliminated ROS in tumor tissues. Besides, e-As
4
S
4
could also inhibit the activation of hypoxia-inducible factor-1α (HIF-1α) and NLRP3 inflammasomes. Consequently, the angiogenesis was reduced, the metastasis to lung and liver was inhibited and the survival of tumor-bearing mice was prolonged. In conclusion, e-As
4
S
4
holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment.
Increasing evidence shows that superparamagnetic scaffolds can enhance the osteogenesis under magnetic fields. The aim of this work is to compare the magnetization and the osteogenic enhancement of superparamagnetic scaffolds composed of different compositions with different microstructures. Herein 9 kinds of superparamagnetic scaffolds of PLA, polyurethane and gelatin were fabricated by incorporating iron oxide nanoparticles in polymeric matrices, and using the process of electrospinning, salt-leaching, and solution casting to obtain microstructure of nanofibrous, porous and smooth respectively, while hydroxyapatite nanoparticles were incorporated in all the scaffolds with the same percentage. It was showed that the magnetization behavior of the scaffolds was associated with the composition and microstructure as well as with the osteogenic enhancement of the scaffolds. The nanofibrous scaffold composed of PLA, nHA and MNPs possessed the strongest magnetization, and significantly promoted the osteogenic differentiation of pre-osteoblasts and bone marrow derived mesenchymal stem cells (bMSCs) under magnetic fields, evidenced by the upregulated gene expression of Runx2 and BMP2, the increased ALP activity, OPN and OCN of the cells. The optimal scaffold recruited more bMSCs and enhanced the osteogenic differentiation and the cross talk among the bMSCs, macrophages and fibroblasts under the magnetic field.
We report that the mass ratio of the polycation to serum in the medium determines the (RNA interference) RNAi efficiency in vitro by using spermine-modified pullulan (Ps) and spermine-modified dextran (Ds) as polycation models. The high ratio of Ps to serum protein (Ps/Pr) mediated the formation of larger polyplexes, which led to the promoted cellular uptake, enhanced lysosomal escape, and elevated RNAi efficiency. In addition, the supplementary of free Ps also enhanced small interfering RNA transfection because of the elevation of Ps/Pr. Similar results were obtained with Ds. Compared with the adjustment of the nitrogen to phosphate (N/P) ratio in the polyplex, these findings revealed a more applicable strategy to tune the polycation-mediated RNAi efficiency in the serum-containing culture medium.
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