Procyanidins inhibit tumor angiogenesis by crosslinking extracellular matrix.

OBJECTIVE: Procyanidins (PC) are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix (ECM) and preventing proteolysis by matrix metalloproteinases (MMPs). METHODS: Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma. RESULTS: PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC (0.75-100 µg/ml) did not inhibit vascular and tumor cells proliferation. PC injections (30 mg PC/kg bodyweight) in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs. CONCLUSION: The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.

Flower-like hierarchically nanostructured hydroxyapatite hollow spheres: facile preparation and application in anticancer drug cellular delivery.

Flower-like nanostructured hydroxyapatite hollow spheres (NHHS) assembled with nanosheets with a hierarchical morphology are fabricated by a rapid microwave-assisted hydrothermal route. The presence and concentration of block copolymer poly(lactide)-block-poly(ethylene glycol) (PLA-PEG) are important parameters for the formation of the hollow structure. The possible formation mechanism of NHHS is proposed. The NHHS are explored as anticancer drug carriers for cellular delivery of mitoxantrone (MIT). The MIT-loaded NHHS exhibit sustained-drug-release behavior in vitro and the intracellular drug-distribution tests indicate that the MIT loaded in NHHS carriers can enter the cells efficiently. The experiments also show that the NHHS have a good biocompatibility, and therefore, they are promising anticancer drug carriers in cancer chemotherapy.

Hydroxyapatite nanorods/poly(vinyl pyrolidone) composite nanofibers, arrays and three-dimensional fabrics: electrospun preparation and transformation to hydroxyapatite nanostructures.

Electrospinning has been recognized as an efficient technique for fabricating polymer nanofibrous biomaterials. However, the study of electrospun inorganic biomaterials with well-designed three-dimensional (3-D) structures is still limited and little reported. In this study hydroxyapatite (HAp) nanorods with an average diameter of approximately 7 nm and length of approximately 27 nm were synthesized through a simple precipitation method and used for the fabrication of inorganic/organic [poly(vinyl pyrolidone) (PVP)] composite nanofibers by electrospinning in ethanol solution. 3-D fabrics and aligned nanofiber arrays of the HAp nanorods/PVP composite were obtained as precursors. Thereafter, 3-D single phase HAp fabrics, tubular structures and aligned nanofiber arrays were obtained after thermal treatment of the corresponding composite precursors. Cytotoxicity experiments indicated that the HAp fabric scaffold had good biocompatibility. In vitro experiments showed that mesenchymal stem cells could attach to the HAp fabric scaffold after culture for 24h.

Characterization and in vitro bioactivity of zinc-containing bioactive glass and glass-ceramics.

Zinc-containing glass is prepared by the substitution of CaO in 58S bioactive glass with 0.5 and 4 wt% ZnO, and glass-ceramics are obtained by heat-treating the glass at 1,200 C. The bending strength and in vitro bioactivity of the glass and glass-ceramics are evaluated. The results indicate that Zn promotes the crystallization of SiO(2) and wollastonite in glass-ceramics, and proper crystallization can enhance the bending strength of the glass-ceramic. The in vitro results show that ZnO in glass retards the hydroxyapatite (HA) nucleation at the initial stage of simulated body fluid (SBF) soaking, but does not affect the growth of HA after long periods of soaking, and the ionic products of 58S4Z glass can stimulate the proliferation of osteoblast at certain concentrations. Osteoblasts attach well on both glass samples and glass-ceramic samples, but the high Si ion concentration released from glass samples restrains the proliferation of osteoblasts after 3 days of culture. In contrast, osteoblasts show good proliferation on glass-ceramic samples, and ZnO in glass-ceramics promotes the proliferation rate. The results in this study suggest that the glass and glass-ceramics with different ZnO content might be used as bioactive bone implant materials in different applications.