Monday, September 11, 2017

PLGA-PEG-Mal from PolySciTech used in the development of Fn14-targeting nanoparticle system for brain cancer treatment


Glioblastoma accounts for 12-15% of all intracranial (brain) tumors. This particular form of brain-cancer is resistant to conventional therapies and tends to be rapidly growing, which makes this form of cancer particularly difficult to treat. Recently, researchers at the University of Maryland used mPEG-PLGA (PolyVivo# AK010) PLGA-PEG-Maleimide (PolyVivo# AI053), and PLGA-Rhodamine B (PolyVivo# AV011) from PolySciTech (www.polyscitech.com) to develop nanoparticles which bind strongly to the Fn14 receptor that is found in brain-cancer. This research holds promise to provide for additional treatment options to this deadly disease. Read more: Wadajkar, Aniket S., Jimena G. Dancy, Nathan B. Roberts, Nina P. Connolly, Dudley K. Strickland, Jeffrey A. Winkles, Graeme F. Woodworth, and Anthony J. Kim. "Decreased non-specific adhesivity, receptor targeted (DART) nanoparticles exhibit improved dispersion, cellular uptake, and tumor retention in invasive gliomas." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917308295

“Abstract: The most common and deadly form of primary brain cancer, glioblastoma (GBM), is characterized by significant intratumoral heterogeneity, microvascular proliferation, immune system suppression, and brain tissue invasion. Delivering effective and sustained treatments to the invasive GBM cells intermixed with functioning neural elements is a major goal of advanced therapeutic systems for brain cancer. Previously, we investigated the nanoparticle characteristics that enable targeting of invasive GBM cells. This revealed the importance of minimizing non-specific binding within the relatively adhesive, ‘sticky’ microenvironment of the brain and brain tumors in particular. We refer to such nanoformulations with decreased non-specific adhesivity and receptor targeting as ‘DART’ therapeutics. In this work, we applied this information toward the design and characterization of biodegradable nanocarriers, and in vivo testing in orthotopic experimental gliomas. We formulated particulate nanocarriers using poly(lactic-co-glycolic acid) (PLGA) and PLGA-polyethylene glycol (PLGA-PEG) polymers to generate sub-100 nm nanoparticles with minimal binding to extracellular brain components and strong binding to the Fn14 receptor – an upregulated, conserved component in invasive GBM. Multiple particle tracking in brain tissue slices and in vivo testing in orthotopic murine malignant glioma revealed preserved nanoparticle diffusivity and increased uptake in brain tumor cells. These combined characteristics also resulted in longer retention of the DART nanoparticles within the orthotopic tumors compared to non-targeted versions. Taken together, these results and nanoparticle design considerations offer promising new methods to optimize therapeutic nanocarriers for improving drug delivery and treatment for invasive brain tumors. Graphical abstract: Fn14-targeted nanoparticles bind specifically to Fn14 receptor but not to brain ECM and are retained in invasive intracranial tumors over significantly longer periods than non-targeted nanoparticles. Keywords: Glioblastoma; Invasive malignant glioma; Biodegradable nanoparticles; Targeted therapeutics; Fibroblast growth factor-inducible 14; Multiple particle tracking; Surface plasmon resonance”
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