Search

The delivery of mesothelial cells by nanofibrous membranes (NFMs) can repair a damaged peritoneal mesothelium and enhance peritoneal healing in patients with chronic renal failure. On the other hand, the orientation of the nanofibers in NFMs may affect cell attachment, proliferation, and the phenotype of mesothelial cells in the nanostructured scaffold. We prepare composite gelatin/chitosan NFMs with aligned or random fiber orientations by electrospinning. We cross-link the nanofibers to maintain the fiber orientation during in vitro cell culture. We then study the cellular response of attached mesothelial cells to fiber orientation in the scaffold. From in vitro cell culture with rat mesothelial cells, the prepared NFMs show high biocompatibility to support cellular growth, regardless of fiber orientation. However, the alignment of electrospun nanofibers in a well-defined geometry can promote cell adhesion and proliferation rates with directional cell organization. The anisotropic arrangement of mesothelial cells in the aligned NFM also coincides with the phenotypic maintenance of the attached mesothelial cells, with biophysical cues provided by the aligned nanofibers. The aligned NFMs may find applications in tissue engineering of a damaged mesothelium layer or in other regenerative therapies where cellular alignment is critical for neo-tissue regeneration. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most severe form of brain cancer and presents unique challenges to developing novel treatments due to its immunosuppressive milieu where receptors like programmed death ligand 1 (PD-L1) are frequently elevated to prevent an effective anti-tumor immune response. To potentially shift the GBM environment from being immunosuppressive to immune-enhancing, we engineered a novel nanovehicle from reduced graphene oxide quantum dot (rGOQD), which are loaded with the immunomodulatory drug resiquimod (R848) and conjugated with an anti-PD-L1 antibody (aPD-L1). The immunomodulatory rGOQD/R8/aPDL1 nanoparticles can actively target the PD-L1 on the surface of ALTS1C1 murine glioblastoma cells and release R848 to enhance the T-cell-driven anti-tumor response. From in vitro experiments, the PD-L1-mediated intracellular uptake and the rGOQD-induced photothermal response after irradiation with near-infrared laser light led to the death of cancer cells and the release of damage-associated molecular patterns (DAMPs). The combinational effect of R848 and released DAMPs synergistically produces antigens to activate dendritic cells, which can prime T lymphocytes to infiltrate the tumor in vivo. As a result, T cells effectively target and attack the PD-L1-suppressed glioma cells and foster a robust photothermal therapy elicited anti-tumor immune response from a syngeneic mouse model of GBM with subcutaneously implanted ALTS1C1 cells. [ABSTRACT FROM AUTHOR]