ORCID Profile
0000-0003-2353-7508
Current Organisation
Université de Fribourg Adolphe Merkle Institute
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Publisher: Wiley
Date: 23-09-2015
Abstract: Mesoporous silica nanoparticles (MSNPs), 100 nm in size, incorporating a Cy5 fluorophore within the silica framework, are synthesized and loaded with the anti-cancer drug temozolomide (TMZ), used in the treatment of gliomas. The surface of the particles is then decorated, using electrostatic interactions, with a polyarginine-peptide nucleic acid (R8-PNA) conjugate targeting the miR221 microRNA. The multi-functional nanosystem thus obtained is rapidly internalized into glioma C6 or T98G cells. The anti-miR activity of the PNA is retained, as confirmed by reverse transcription polymerase chain reaction (RT-PCR) measurements and induction of apoptosis is observed in temozolomide-resistant cell lines. The TMZ-loaded MSNPs show an enhanced pro-apoptotic effect, and the combined effect of TMZ and R8-PNA in the MSNPs shows the most effective induction of apoptosis (70.9% of apoptotic cells) thus far achieved in the temozolomide-resistant T98G cell line.
Publisher: Wiley
Date: 08-12-2015
Abstract: The direct delivery of specific proteins to live cells promises a tremendous impact for biological and medical applications, from therapeutics to genetic engineering. However, the process mostly involves tedious techniques and often requires extensive alteration of the protein itself. Herein we report a straightforward approach to encapsulate native proteins by using breakable organosilica matrices that disintegrate upon exposure to a chemical stimulus. The biomolecule-containing capsules were tested for the intracellular delivery of highly cytotoxic proteins into C6 glioma cells. We demonstrate that the shell is broken, the release of the active proteins occurs, and therefore our hybrid architecture is a promising strategy to deliver fragile biomacromolecules into living organisms.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1TB00721A
Abstract: The efficiency of metabolic labelling and click-chemistry to attach nanoparticles to cell surfaces is different between different cell populations in co-culture formats.
Publisher: Wiley
Date: 03-2020
Publisher: eLife Sciences Publications, Ltd
Date: 07-10-2020
DOI: 10.7554/ELIFE.59442
Abstract: The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived s les, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.
Publisher: Wiley
Date: 02-05-2014
Abstract: The design and synthesis of smart nanomaterials can provide interesting potential applications for biomedical purposes from bioimaging to drug delivery. Manufacturing multifunctional systems in a way to carry bioactive molecules, like peptide nucleic acids able to recognize specific targets in living cells, represents an achievement towards the development of highly selective tools for both diagnosis and therapeutics. This work describes a very first ex le of the use of zeolite nanocrystals as multifunctional nanocarriers to deliver simultaneously PNA and organic molecules into living cells. Zeolite-L nanocrystals are functionalized by covalently attaching the PNA probes onto the surface, while the channel system is filled with fluorescent guest molecules. The cellular uptake of the PNA/Zeolite-L hybrid material is then significantly increased by coating the whole system with a thin layer of biodegradable poly-L-lysine. The delivery of DAPI as a model drug molecule, inserted into the zeolite pores, is also demonstrated to occur in the cells, proving the multifunctional ability of the system. Using this zeolite nanosystem carrying PNA probes designed to target specific RNA sequences of interest in living cells could open new possibilities for theranostic and gene therapy applications.
Publisher: Public Library of Science (PLoS)
Date: 03-12-2020
DOI: 10.1371/JOURNAL.PONE.0241500
Abstract: The presence of ascites in the peritoneal cavity leads to morphological and functional changes of the peritoneal mesothelial cell layer. Cells loose cell-cell interactions, rearrange their cytoskeleton, activate the production of fibronectin, and change their cell surface morphology in a proinflammatory environment. Moreover, ovarian cancer cell adhesion has been shown to be facilitated by these changes due to increased integrin- and CD44-mediated binding sites. In this study, the biological responsiveness of the human pleural mesothelial cell line MeT-5A to patient-derived and artificial ascites was studied in vitro and adhesion of ovarian cancer cells, i.e. SKOV-3 cells, investigated. Changes were mainly observed in cells exposed to artificial ascites containing higher cytokine concentrations than patient-derived ascites. Interestingly, reduced cell-cell interactions were already observed in untreated MeT-5A cells and effects on tight junction protein expression and permeability upon exposure to ascites were minor. Ascites induced upregulation of CDC42 effector protein 2 expression, which affects stress fiber formation, however significant F-actin reorganization was not observed. Moreover, fibronectin production remained unchanged. Analysis of mesothelial cell surface characteristics showed upregulated expression of intercellular adhesion molecule 1, slightly increased hyaluronic acid secretion and decreased microvillus expression upon exposure to ascites. Nevertheless, the observed changes were not sufficient to facilitate adhesion of SKOV-3 cells on MeT-5A cell layer. This study revealed that MeT-5A cells show a reduced biological responsiveness to the presence of ascites, in contrast to published studies on primary human peritoneal mesothelial cells.
Publisher: Wiley
Date: 08-07-2014
Abstract: The design and synthesis of multifunctional nanomaterials could lead to applications relevant for biomedicine. Manufacturing porous particles to make them able to carry bioactive molecules into living cells represents a substantial goal towards the development of powerful tools for nanomedicine. This work describes a first ex le of using zeolite-L crystals as multifunctional nanocontainers to simultaneously deliver DNA oligonucleotides and organic molecules into living cells. Multifunctional zeolite-L was prepared by filling the pore system with guest molecules, whilst DNA was adsorbed electrostatically on their surface. The release kinetics of DNA and of the guest molecules into living cells was studied to prove the multiple-drug-delivery ability of the system. The localization of all the components in different cellular compartments was followed. The presented system may be a prototype for the development of novel nanoparticles for drug delivery and gene therapy.
Location: Switzerland
No related grants have been discovered for Dedy Septiadi.