Sendai virus-based liposomes enable targeted cytosolic delivery of nanoparticles in brain tumor-derived cells

Abstract

BackgroundNanotechnology-based bioassays that detect the presence and/or absence of a combination of cell markers are increasingly used to identify stem or progenitor cells, assess cell heterogeneity, and evaluate tumor malignancy and/or chemoresistance. Delivery methods that enable nanoparticles to rapidly detect emerging, intracellular markers within cell clusters of biopsies will greatly aid in tumor characterization, analysis of functional state and development of treatment regimens.ResultsExperiments utilized the Sendai virus to achieve in vitro, cytosolic delivery of Quantum dots in cells cultured from Human brain tumors. Using fluorescence microscopy and Transmission Electron Microscopy, in vitro experiments illustrated that these virus-based liposomes decreased the amount of non-specifically endocytosed nanoparticles by 50% in the Human glioblastoma and medulloblastoma samples studied. Significantly, virus-based liposome delivery also facilitated targeted binding of Quantum dots to cytosolic Epidermal Growth Factor Receptor within cultured cells, focal to the early detection and characterization of malignant brain tumors.ConclusionsThese findings are the first to utilize the Sendai virus to achieve cytosolic, targeted intracellular binding of Qdots within Human brain tumor cells. The results are significant to the continued applicability of nanoparticles used for the molecular labeling of cancer cells to determine tumor heterogeneity, grade, and chemotherapeutic resistivity.

Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells

“…Next, MB-derived cells were incubated with Transferrin (Tf), a marker of the clathrin-mediated endocytic pathway and Cholera Toxin Subunit-B (CT-B), a marker of the clathrin-independent endocytic pathway, as done previously by our group. 8 In MB-derived cells, iEGF-R was seen to co-localize predominantly with Tf: 92 ± 3% (Figs. 2i1–3 and 2j), but only 14 ± 4% with CT-B (Fig.…”

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

“…Specific targeting of EGFR + U87 cells; inhibition of U87 cell growth; specific targeting of glioma CSCs not reported [100] IONPs conjugated to the EGFR inhibitor cetuximab (Cet-IONPs) Targeting of CD133-independent glioma cells; alteration of EGFR signalling; internalization of EGFR; apoptosis of EGFR + GBM CSCs and neurospheres; increased survival of GBM xenografted rodents upon CEDadministered Cet-IONPs [101] Sendai virus-based liposomes containing Qdots specific to cytosolic EGFR Specific binding of Qdots to intracellular EGFR in GBM and medulloblastoma cell cultures in vitro [102] Polyethylene glycol-poly(lactic-co-glycolic acid) NPs conjugated to Pep-1 (a IL13Rα2 ligand) (Pep-NPs) Efficient targeting of rat C6 glioma cells and penetration into 3D avascular C6 glioma spheroids; this formulation does not allow to selectively target GBM CSCs [103] NPs functionalized with IL-13 and loaded with docetaxel (IL-13-NPs)…”

“…Additionally, Sendai virus-based liposomes have been applied to achieve the targeted binding of Qdots NPs specifically to cytosolic EGFR within GBM and medulloblastoma cell cultures in vitro, as shown by means of fluorescence microscopy and transmission electron microscopy, this representing an efficient method for the early detection of brain tumors [102].…”

pH-sensitive polymer-modified liposome-based immunity-inducing system: Effects of inclusion of cationic lipid and CpG-DNA

“…Among them, lipid-based antigen delivery carriers are particularly useful because they can induce membrane fusion or destabilization of endosomal membrane and can achieve cytoplasmic delivery of antigen. Typical examples of cytoplasmic delivery systems using lipid-based carrier are viral fusogenic protein-incorporated liposomes such as Sendai virus-derived fusogenic protein-introduced liposomes [5] or Virosome, influenza virus fusogenic protein (hemagglutinin)-incorporated liposomes [6].…”