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PEGylated and folate-targeted chitosan polymeric nanoparticles (FPNs) for the treatment of gastric carcinoma were prepared successfully. OQC-anchored folate conjugates were synthesized and used in assembling FPNs nano-system for enhancing intracellular uptake against folate receptor overexpressing cancer cells. The results indicated that folate-targeted chitosan polymeric nanoparticles (CPNs) can reverse drug-resistant SGC-7901 cells of 5-fluorouracil (5-FU) compared with non-targeted CPNs. Increased therapeutic efficiency of 5-FU/METHFR shRNA co-loaded PNs were also tested in SGC-7901 cells and compaed with 5-FU or METHFR shRNA in solution, which was associated with increased cell inhibition function for single drug group and synergistic effects of 5-FU and METHFR shRNA at 2.0 µg/mL FPNs concentration. In addition, the cell accumulation levels of 5-FU in SGC-7901 cells was time dependent for these nanoparticles. FPNs (effective diameter: 83.2 ± 1.1 nm; polydispersity index: 0.193) could significantly boost cellular accumulation of 5-FU and overcome the drug efflux mechanism of MDR than 5-FU-loaded NPNs and 5-FU in solution. In conclusion, ligand-targeted PNs can be used as a potentially effective drug delivery system. [ABSTRACT FROM AUTHOR]

In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration. [ABSTRACT FROM AUTHOR]