Catherine Carmichael

Low-Fouling and Biodegradable Protein-Based Particles for Thrombus Imaging

Nanomedicine holds great promise for vascular disease diagnosis and specific therapy, yet rapid sequestration by the mononuclear phagocytic system limits the efficacy of particle-based agents. The use of low-fouling polymers, such as poly(ethylene glycol), efficiently reduces this immune recognition, but these nondegradable polymers can accumulate in the human body and may cause adverse effects after prolonged use. Thus, new particle formulations combining stealth, low immunogenicity and biocompatible features are required to enable clinical use. Here, a low-fouling particle platform is described using exclusively protein material. A recombinant protein with superior hydrophilic characteristics provided by the amino acid repeat proline, alanine, and serine (PAS) is designed and cross-linked into particles with lysine (K) and polyglutamic acid (E) using mesoporous silica templating. The obtained PASKE particles have low-fouling behavior, have a prolonged circulation time compared to albumin-based particles, and are rapidly degraded in the cells lysosomal compartment. When labeled with near-infrared fluorescent molecules and functionalized with an anti-glycoprotein IIb/IIIa single-chain antibody targeting activated platelets, the particles show potential as a noninvasive molecular imaging tool in a mouse model of carotid artery thrombosis. The PASKE particles constitute a promising biodegradable and versatile platform for molecular imaging of vascular diseases.

MOESM18 of Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing

Additional file 18. shRNA Sequences. 97-mer shRNA oligonucleotides used to create the retroviral shRNAsÂxa0for the X inactivation screen and additional hairpins used in this study. The common miR30 5â , loop and 3â sequences are in black, the unique 21-mer stem sequences are in red and theÂxa0mismatched bases are in blue.