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Frasch, L.

Publications and source records attributed to Frasch, L..

2 recordsLinked to original sources

Development of a PEGylated Parylene Nanopocket Membrane for the Capture and Release of Lipid Vesicles

Membranes are commonly used for the separation and purification of a variety of biological species. In this study, we developed a nanopocket membrane that can capture nanoparticles and extracellular vesicles in tangential flow filtration by pulling the species of interest into a nanopocket, while tangential flow washes away particles too large to be captured. We developed the pores using a four-step lithography process. By optimizing photolithography parameters, particularly exposure dose, we achieved well-defined pore shapes with the desired wall tilt, forming nanopocket geometries. We validated membrane performance using bead mixtures of varying diameters (50 nm -10 {micro}m), demonstrating its ability to pass small particles, capture mid-sized particles, and exclude larger ones. Surface modification with poly(l-lysine)- grafted poly(ethylene glycol) enhanced this performance by reducing pore size and improving particle release. Additionally, we demonstrated selective capture and release of liposomes as well as EVs in the presence of fluorescently labeled BSA (f-BSA) protein. During this process, EVs were retained and later released, while f-BSA passed through, confirming selective capture and reduced protein contamination. These PEGylated nanopocket membranes constitute a low-pressure platform for gentle, size-selective isolation of nanoscale bioparticles, laying the groundwork for improved extracellular-vesicle analytics and point-of-care diagnostic applications.

bioengineering↗

Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response

The DNA-damaging agent gemcitabine (GEM) is a first-line treatment for pancreatic cancer but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs including kinase inhibitors but the experimental evidence for such rational is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 140 clinical kinase inhibitors and observed strong synergy for the ATR inhibitor Elimusertib in most cell lines. Dose-dependent phosphoproteome profiling of four ATR inhibitors following DNA damage induction by GEM revealed a strong block of the DNA damage response pathway including phosphorylated pS468 of CHEK1 as the underlying mechanism of drug synergy. The current work provides a strong rationale for why the combination of GEM and ATR inhibition may be useful for the treatment of PDAC patients and constitutes a rich phenotypic and molecular resource for further investigating effective drug combinations.

cancer biology↗