Simultaneous elimination of cancer stem cells and bulk cancer cells by cationic-lipid-assisted nanoparticles for cancer therapy

Convincing evidence indicates that the existence of cancer stem cells （CSCs） within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, simultaneous elimin- ation of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanopartides DTXLNPsRNA for simultaneous encapsulation of the conventional chemotherapeutic agent docetaxel （DTXL） and small interfering RNA （siRNA） targeting BMI-1 （siBMI-1）. We confirmed that nanopartides vrxLNPsiBMI-l effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DVXL NPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DVXLNpsiBMI-1; consequently, the sternness was reduced and chemosensitivity of CSCs to DTXL was enhanced, resulting in the elimination of CSCs. Therefore, via DTXLNPsiBMI-1, the combination of siBMI-1 and DTXL completely inhibited tumor growth and prevented a relapse by synergistic kiUing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.

Surface Bioactive Modification of Alumina Ceramic by Mineralization in Modified SBF

In the present study,it is found that the prepared alumina ceramics has better mineralization ability in a newly revised simulated body fluid.With the extension of mineralization time,the amount of hydroxyapatite(HA)crystals deposited on the surface of alumina ceramics also increased gradually.The results of cell biological experiments of alumina ceramics with hydroxyapatite surface layer demonstrate that the mineralized materials have better biological activity and osteogenesis properties in vitro.In the meanwhile,the ALP activity and expression of osteogenesis-related genes(OPN,ALP,Col-I,and OCN)of mouse bone marrow stromal stem cells on the samples were significantly promoted by increasing the formation of HA on the surface of alumina ceramics.Our research concluded that alumina ceramics with HA phase on surface had great potential to be developed as a sort of bioactive material in the bone repair field.

Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis

Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （siRNAs） for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly（ethylene glycol）-block-poly（lactic-co-glycolic acid） （PEG5K-b-PLGA10K） NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs （ANPs）, plain NPs （PNPs）, or carboxylated NPs （CNPs） based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-α secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis （UC）. This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.