(558a) miRNA Loading and Release Behavior of Dual Stimuli-Responsive Polycationic Nanoparticles in the Treatment of Glioblastoma Multiforme

MicroRNA therapy, based on the RNA-interference mechanism present in all mammalian cells, has received great interest for its potential in cancer treatment. However, clinical translation has been limited due to challenges associated with the controlled delivery of nanoparticles to target cells. Here, we are assessing the microRNA loading and release behavior of a dual stimuli-responsive polycationic nanoparticle system for the treatment of glioblastoma multiforme. Diethylaminoethyl methacrylate (DEAEMA)-based nanoparticles were synthesized via activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). By using the pH-responsive monomer, DEAEMA, we have developed carriers that remain collapsed at physiological pH and swell in more acidic conditions. ¹³C Nuclear Magnetic Resonance (NMR) was conducted using a 400MHz NMR (Agilent MR400). Nanoparticle hydrodynamic diameter and zeta potential was measured using a Malvern Zetasizer NanoZS with an MPT-2 multi-purpose titrator. MicroRNA loading and release efficiency was determined via Qubit fluorometric quantification. Polycationic nanoparticle formulations were incubated with microRNA mimics in 1X PBS at varying pH. Release behavior was assessed at physiological pH and acidic pH. Glioma stem cell line, GSC3565, was used as a model cell line to assess transfection. Incucyte proliferation assays were used to visualize miRNA mimic release and cellular uptake by GSC3565 cells.