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Engineering Discoidal Polymeric Nanoconstructs for the Multi-Physics Treatment of Brain Tumors

Mid-Term Report Summary - POTENT (Engineering Discoidal Polymeric Nanoconstructs for the Multi-Physics Treatment of Brain Tumors)

The project POTENT has the objective of developing polymeric nanoconstructs for the imaging and treatment of brain tumors. This mid-term report documents the fabrication of discoidal polymeric nanoconstructs (DPNs) for the specific delivery of therapeutic and imaging agents; the development of computational models for the in silico optimization of the vascular behavior of systemically injected DPNs; the design and implementation of microfluidic chips for the in vitro analysis of the vascular transport and adhesion of circulating DPNs; the analysis of DPN biodistribution and interaction with cells of the immune system. Specifically, 12 different configurations of DPNs have been fabricated and characterized: 1.0 and 2.0 µm circular DPNs, 2.0 x 1.5 µm elliptical DPNs; and 1.0 µm square DPNs with soft (100 kPa), rigid (1.0 MPa) and rigid-rigid structures (10 MPa). In silico and in vitro experiments continue to confirm that soft DPNs can more efficiently recognize the tumor vasculature and evade recognition by cells of the immune system. Thus, soft DPNs present the best ratio between tumor accumulation and non-specific sequestration into the liver and spleen. Within the second portion of the project, already ongoing studies will help identifying the subset of DPNs with the highest therapeutic efficacy against glioblastoma multiforme.