Interior Engineering of a Viral Nanoparticle and Its Tumor Homing Properties

Abstract

The development of multifunctional nanoparticles for medical applications is of growing technological interest. A single formulation containing imaging and/or drug moieties that is also capable of preferential uptake in specific cells would greatly enhance diagnostics and treatments. There is growing interest in plant-derived viral nanoparticles (VNPs) and establishing new platform technologies based on these nanoparticles inspired by nature. Cowpea mosaic virus (CPMV) serves as the standard model for VNPs. Although exterior surface modification is well known and has been comprehensively studied, little is known of interior modification. Additional functionality conferred by the capability for interior engineering would be of great benefit toward the ultimate goal of targeted drug delivery. Here, we examined the capacity of empty CPMV (eCPMV) particles devoid of RNA to encapsulate a wide variety of molecules. We systematically investigated the conjugation of fluorophores, biotin affinity tags, large molecular weight polymers such as polyethylene glycol (PEG), and various peptides through targeting reactive cysteines displayed selectively on the interior surface. Several methods are described that mutually confirm specific functionalization of the interior. Finally, CPMV and eCPMV were labeled with near-infrared fluorophores and studied side-by-side in vitro and in vivo. Passive tumor targeting via the enhanced permeability and retention effect and optical imaging were confirmed using a preclinical mouse model of colon cancer. The results of our studies lay the foundation for the development of the eCPMV platform in a range of biomedical applications.

Assembly and Purification of Polyomavirus-Like Particles from Plants

“…Indeed, we found that wtVLPs contained DNA, whereas DVLPs did not, which is in agreement with previous findings in insect cells [15]. This is a significant benefit in biotechnology as undefined nucleic acid encapsidation is seen as a contaminant in the case of vaccines and having an empty capsid enables the directed encapsidation of therapeutics and [2,48,50]. Moreover, it seems likely that the elimination of DNA binding also obviated the necrotising effect of wtVP1 on leaf tissue.…”

The study of toxicity and pathogenicity risk of Potato Virus X/Herceptin nanoparticles as agents for cancer therapy

“…Hence, it is necessary to study the toxicity of nanoparticles. Since viruses are self-assembled (Wen et al 2012), stabilized (Steinmetz 2010), and biodegradable (Singh et al 2007), they are expected to be good candidates as drug carriers. Researchers have addressed different uses for these carriers by non-pathogenic viruses.…”

“…Various types of plant viruses are extensively used for VNPs (Culver et al 2015;Lico et al 2015). Although filamentous and rod-shaped VNPs have increased tumor homing properties, most of the studies conducted in nanomedicine application have focused more on spherical plant virus (Biabanikhankahdani et al 2016;Bruckman et al 2014;Le et al 2017;Shukla et al 2013;Wen et al 2012). Regarding targeted drug delivery, the use of VNPs in transferring therapeutic products to specific cells to treat cancer and infectious diseases is considered as one of the emerging fields.…”

A new application of plant virus nanoparticles as drug delivery in breast cancer

“…As a nano carrier, VNPs have many favorable properties such as self assembly, stability, [3] produced large quantities in short time [6], biodegradable, and non-toxicity in mammals [20].…”

“…Many different platforms have been developed, including synthetic nanomaterials and naturally bionanomaterials such as viral nanoparticles (VNPs). VNPs are one of the biggest groups of bionanoparticles which originated from plant, animal, or bacterial viruses [3]. Biocompatibility and biodegradability of VNPs offer advantages over synthetic nanoparticles.…”