Shaping bio-inspired nanotechnologies to target thrombosis for dual optical-magnetic resonance imaging

Abstract

Arterial and venous thrombosis are among the most common causes of death and hospitalization worldwide. Nanotechnology approaches hold great promise for molecular imaging and diagnosis as well as tissue-targeted delivery of therapeutics. In this study, we developed and investigated bioengineered nanoprobes for identifying thrombus formation; the design parameters of nanoparticle shape and surface chemistry, i.e. incorporation of fibrin-binding peptides CREKA and GPRPP, were investigated. Two nanoparticle platforms based on plant viruses were studied — icosahedral cowpea mosaic virus (CPMV) and elongated rod-shaped tobacco mosaic virus (TMV). These particles were loaded to carry contrast agents for dual-modality magnetic resonance (MR) and optical imaging, and both modalities demonstrated specificity of fibrin binding in vitro with the presence of targeting peptides. Preclinical studies in a carotid artery photochemical injury model of thrombosis confirmed thrombus homing of the nanoprobes, with the elongated TMV rods exhibiting significantly greater attachment to thrombi than icosahedral (sphere-like) CPMV. While in vitro studies confirmed fibrin-specificity conferred by the peptide ligands, in vivo studies indicated the nanoparticle shape had the greatest contribution toward thrombus targeting, with no significant contribution from either targeting ligand. These results demonstrate that nanoparticle shape plays a critical role in particle deposition at the site of vascular injury. Shaping nanotechnologies opens the door for the development of novel targeted diagnostic and therapeutic strategies (i.e., theranostics) for arterial and venous thrombosis.

The effects of particle size, shape, density and flow characteristics on particle margination to vascular walls in cardiovascular diseases

“…The lower adhesion of AR9 rods compared to AR4 rods, despite their higher contact surface area, is likely due to their entrapment in the capillaries as AR9 rods have a major axis length of roughly 9 μm [15]. Recently, Wen et al have also demonstrated that rod-shaped particles (elongated TMV) functionalized with binding peptides and contrast agents (gadolinium) could be targeted to activated platelets/thrombus in mouse carotid artery at a higher magnitude compared to sphere-like particles (icosahedral cowpea mosaic virus) [89].…”

Design of virus-based nanomaterials for medicine, biotechnology, and energy

“…147 Some other advantageous properties that are conferred by elongated particles include better margination toward the vessel wall and stronger adherence due to greater surface area for interaction, which not only have implications for tumor homing but also for enhanced targeting of cardiovascular disease. 148, 149 …”

Self-assembling peptide-based building blocks in medical applications

“…The majority of studies focus on cardiovascular and cancer detection. Although other supramolecular nanoparticles such as liposomes, viral capsids, and nanoemulsions incorporate peptide conjugates, peptides are often added after self-assembly of the particle, and we refer the reader to other recent articles and reviews [141–144]. …”