A smart upconversion-based light-triggered polymer for synergetic chemo-photodynamic therapy and dual-modal MR/UCL imaging.

We have developed a novel nanocomposite to achieve effective therapy and live surveillance of tumor tissue. In this study, fullerene (C60) with iron oxide (Fe3O4) nanoparticles and upconversion nanophosphors (UCNPs) was loaded into N-succinyl-N'-4-(2-nitrobenzyloxy)-succinyl-chitosan micelles (SNSC) with good biocompatibility. In addition, hydrophobic anticancer drug docetaxel (DTX) was also loaded into the nanocomposites. The experiments conducted in vitro and in vivo demonstrated that C60/Fe3O4-UCNPs@DTX@SNSC can act synergistically to kill tumor cells by releasing chemotherapy drugs at specific target site as well as generating reactive oxygen using 980nm. In addition, it can also be used for non-invasive deep magnetic resonance and upconversion fluorescence dual-mode imaging. The results indicated that this system provided an efficient method to surmount the drawback of UV or visible light-responsive polymeric systems for controlled drug release and generated reactive oxygen in deep tissues and ultimately realized the integration of dual-modal imaging and treatment.

Stem-cell based soft tissue substitutes: Engineering of crosslinked polylysine-hyaluronic acid microspheres ladened with gingival mesenchymal stem cells for collagen tissue regeneration and angiogenesis.

BACKGROUND: The aim of this study was to construct crosslinked polylysine-hyaluronic acid microspheres (pl-HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration. METHODS: The effects of the crosslinked pl-HAM on the biocompatibility and the recruitment of L-929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl-HAMs. RESULTS: The crosslinked pl-HAMs appeared to be completely spherical-shaped particles and had good biocompatibility. L-929 cells and GMSCs grew around the pl-HAMs and increased gradually. Cell migration experiments showed that pl-HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the green fluorescent protein-GMSCs in the pl-HAM group still remain in the soft tissue regeneration area 2 weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis-related indicator CD31 expression in the pl-HAMs+ GMSCs + GeL group compared with the pl-HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co-staining positive cells surrounded the microspheres in both pl-HAMs + GeL group and pl-HAM + GMSCs + GeL group. CONCLUSIONS: The crosslinked pl-HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future.