Designing S100A9-Targeted Plant Virus Nanoparticles to Target Deep Vein Thrombosis

Abstract

Thromboembolic conditions are a leading cause of death worldwide, and deep vein thrombosis (DVT), or occlusive venous clot formation, is a critical and rising problem that contributes to damage of vital organs, long-term complications, and life-threatening conditions such as pulmonary embolism. Early diagnosis and treatment are correlated to better prognosis. However, current technologies in these areas, such as ultrasonography for diagnostics and anticoagulants for treatment, are limited in terms of their accuracy and therapeutic windows. In this work, we investigated targeting myeloid related protein 14 (MRP-14, also known as S100A9) using plant virus-based nanoparticle carriers as a means to achieve tissue specificity aiding prognosis and therapeutic intervention. We used a combinatorial peptide library screen to identify peptide ligands that bind MRP-14. Candidates were selected and formulated as nanoparticles by using cowpea mosaic virus (CPMV) and tobacco mosaic virus (TMV). Intravascular delivery of our MRP-14-targeted nanoparticles in a murine model of DVT resulted in enhanced accumulation in the thrombi and reduced thrombus size, suggesting application of nanoparticles for molecular targeting of MRP-14 could be a promising direction for improving DVT diagnostics, therapeutics, and therefore prognosis.

The International Society of RNA Nanotechnology and Nanomedicine (ISRNN): The Present and Future of the Burgeoning Field

“…Markita Landry at the University of California, Berkeley, has tested carbon nanotubes, DNA, and metal nanoparticles as possible delivery vehicles to get RNA to plants. − Jason White at the Connecticut Agricultural Experiment Station and Yukui Rui at China Agricultural University and their co-workers explore nanodelivery to address pathogenic plant viruses . Nicole Steinmetz, now at the University of California, San Diego, explores nanodelivery to plants and also using plant viruses and parts of plant viruses to treat diseases in humans. , …”

“…147 Nicole Steinmetz, now at the University of California, San Diego, explores nanodelivery to plants 148 and also using plant viruses and parts of plant viruses to treat diseases in humans. 149,150 IMMUNOMODULATION AND IMMUNOTHERAPY WITH NUCLEIC ACID NANOPARTICLES Experimental evidence is growing for the use of NANPs in medical applications, including but not limited to gene deliveries and controlled immunomodulation. Achievements in design principles, manufacturing, creating split functionalities, and delivery strategies of NANPs have created opportunities to use these materials in vaccines, immunotherapies, and other therapeutic applications.…”

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold

“…In recent years, great progress has been made in the research and development of anti-plant virus agents (Carli et al, 2010; Li and Song, 2017 ; Park et al, 2021 ). The discovery of some new antiviral agents based on natural products ( Figure 1B ) not only reflects the important role of natural products in the discovery of antiviral agents, but also provides great help for the control of plant viruses.…”

Metastatic Colon Cancer Treatment Using S100A9-Targeted Cowpea Mosaic Virus Nanoparticles

“…26 We have also explored S100A9 targeting in cardiovascular disease using other S100A9-targeting peptides and the viruses CPMV and the tobacco mosaic virus, which led to increased viral load within the S100A9-rich deep vein thrombi and reduced thrombotic mass. 28 S100A9 was chosen as the target molecule due to its overexpression in a variety of cancers. 29 S100A9, otherwise known as myeloid-related protein 14, is a calcium-binding damage-associated molecular pattern molecule that works as an immunomodulator in many immune disorders.…”