Enhanced Functional Properties of Three DNA Origami Nanostructures as Doxorubicin Carriers to Breast Cancer Cells.

Previous studies have shown that chemotherapeutic efficacy could be enhanced with targeted drug delivery. Various DNA origami nanostructures have been investigated as drug carriers. Here, we compared drug delivery functionalities of three similar DNA origami nanostructures, Disc, Donut, and Sphere, that differ in structural dimension. Our results demonstrated that Donut was the most stable and exhibited the highest Dox-loading capacity. MUC1 aptamer modification in our nanostructures increased cellular uptake in MUC1-high MCF-7. Among the three nanostructures, unmodified Donut exerted the highest Dox cytotoxicity in MCF-7, and MUC1 aptamer modification did not further improve its effect, implicating that Dox delivery by Donut was efficient. However, all Dox-loaded nanostructures showed comparable cytotoxicity in MDA-MB-231 due to the innate sensitivity of this cell line to Dox. Our results successfully demonstrated that functional properties of DNA origami nanocarriers could be tuned by structural design, and three-dimensional Donut appeared to be the most efficient nanocarrier.

ECM-Body: A Cell-Free 3D Biomimetic Scaffold Derived from Intact Planarian Body.

Extracellular matrix (ECM) plays key roles in shaping fates of stem cells, not only by providing a suitable niche but also by mediating physical and biochemical cues. Despite intensive investigations on regeneration, the roles of ECM in fate determination of stem cells in animals with great regenerative potency, such as planarian, have remained unclear. Here, we developed a method for decellularizing and isolating extracellular matrix from planarians. Although the isolated scaffold appears translucent, it contains all the internal features resembling those of the structure of intact planarians, and we thus called it the "ECM-body". Nuclear staining demonstrated that the ECM-body contains very few or no remaining cells. Histological sections displayed well-preserved morphological integrity of the specimen. Scanning electron microscopy showed a porous surface on the ECM-body, potentially suitable for housing cells. Furthermore, our preliminary experiment suggested that ECM-body can be utilized as a biomimetic scaffold for cell culture as it may support survival of injected neoblasts.

Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α.

Lupeol and stigmasterol, major phytosterols in various herbal plants, possess anti-inflammatory activities and have been proposed as candidates for anti-cancer agents, but their molecular mechanisms are still unclear. Here, we investigated the effects of lupeol and stigmasterol on tumor and endothelial cells in vitro and their anti-cancer activities in vivo. Our results demonstrated that lupeol and stigmasterol suppressed cell viability, migration, and morphogenesis of human umbilical vein endothelial cells (HUVECs) but not cholangiocarcinoma (CCA) cells. Expression analyses showed that the treatment of both compounds significantly reduced the transcript level of tumor necrosis factor-α (TNF-α), and Western blot analyses further revealed a decrease in downstream effector levels of VEGFR-2 signaling, including phosphorylated forms of Src, Akt, PCL, and FAK, which were rescued by TNF-α treatment. In vivo, lupeol and stigmasterol disrupted tumor angiogenesis and reduced the growth of CCA tumor xenografts. Immunohistochemical analyses confirmed a decrease in CD31-positive vessel content and macrophage recruitment upon treatment. These findings indicate that lupeol and stigmasterol effectively target tumor endothelial cells and suppress CCA tumor growth by their anti-inflammatory activities and are attractive candidates for anti-cancer treatment of CCA tumors.