journal article·2018-07-24Open access

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

Thomas Bonnard, Anand Jayapadman, Jasmine A. Putri, Jiwei Cui, Yi Ju, Catherine Carmichael, Thomas A. Angelovich, Stephen H. Cody, Shauna French, Karline Pascaud, Hannah A. Pearce, Shweta Jagdale, Frank Caruso, Christoph E. Hagemeyer

ACS Nano· Volume 12· Issue 7

Abstract

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 cell's 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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Characterization and Applications of Magnetic Nanoparticles · Protease and Inhibitor Mechanisms · Biosensors and Analytical Detection

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Nanobiotechnology Laboratory, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, The University of Melbourne, Parkville 3010, Victoria, Australia

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, and the School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China

Mammalian Functional Genetics Laboratory, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia

Chronic Infectious and Inflammatory Diseases Program, School of Health and Biomedical Sciences, RMIT University, Melbourne 3004, Australia

Life Sciences, Burnet Institute, Melbourne 3004, Victoria, Australia

Monash Micro Imaging, Monash University, Melbourne 3004, Victoria, Australia

Platelets and Thrombosis Laboratory, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia

Funding

FP7 People: Marie-Curie Actions · National Health and Medical Research Council · Australian Research Council · National Heart Foundation of Australia · Central Committee of the Communist Party of China

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