Increased Tumor Homing and Tissue Penetration of the Filamentous Plant Viral Nanoparticle Potato virus X

Abstract

Nanomaterials with elongated architectures have been shown to possess differential tumor homing properties compared to their spherical counterparts. Here, we investigate whether this phenomenon is mirrored by plant viral nanoparticles that are filamentous (Potato virus X) or spherical (Cowpea mosaic virus). Our studies demonstrate that Potato virus X (PVX) and Cowpea mosaic virus (CPMV) show distinct biodistribution profiles and differ in their tumor homing and penetration efficiency. Analogous to what is seen with inorganic nanomaterials, PVX shows enhanced tumor homing and tissue penetration. Human tumor xenografts exhibit higher uptake of PEGylated filamentous PVX compared to CPMV, particularly in the core of the tumor. This is supported by immunohistochemical analysis of the tumor sections, which indicates greater penetration and accumulation of PVX within the tumor tissues. The enhanced tumor homing and retention properties of PVX along with its higher payload carrying capacity makes it a potentially superior platform for applications in cancer drug delivery and imaging applications.

Biodistribution and Clearance of A Filamentous Plant Virus in Healthy and Tumor-Bearing Mice

“…We conjugated PVX with the near-infrared fluorophore A647 to allow the imaging and tracking of the formulations, and also with PEG to enhance particle solubility and stability. A647 and PEG5000 were chosen because we recently showed that A647-PVX-PEG is suitable for tumor homing and imaging in preclinical tumor animal models [9]. We therefore designed the PVX formulation according to our published procedures (Figure 1A) [9].…”

“…Leaves were harvested 10–14 days after mechanical inoculation with 5 μg of purified PVX particles. PVX was purified as described earlier (please see Supplementary Material online at www.futuremedicine.com/doi/suppl/13.75) [9]. …”

“…PVX measures 515 × 13 nm, with a flexible filamentous structure, which is difficult to replicate using synthetic chemistry. In a recent study, we demonstrated that PVX and CPMV have distinct in vivo profiles with CPMV homing predominantly to the liver and, to a lesser extent, the spleen, whereas PVX was predominantly taken up by the spleen and, to a lesser extent, the liver [9]. Significant differences were observed with regard to tumor homing: PVX showed enhanced tumor homing, especially in the core of the tumor xenografts (fibrosarcoma, squamous sarcoma and colon cancer) in both avian and mouse tumor models [9].…”

Production of Immunoabsorbent Nanoparticles by Displaying Single‐Domain Protein A on Potato Virus X

“…We established bioconjugation protocols targeting surface-exposed lysines using N-hydroxysuccinimide or Cu(I)-catalyzed azide-alkyne cycloaddition (click chemistry) enabling efficient functionalization of PVX with biotin linkers, fluorophores, PEG, targeting ligands, etc. [12][13][14][15] To date PVX has been used for epitope presentation approaches in vaccine development; [9,16] chimeric PVX particles have also been combined with enzymes for the fabrication of novel biocatalysts, [17] and PVX is undergoing development as a novel carrier for oncological imaging and therapeutic intervention. [12][13][14][15] To extend the application of PVX, we set out to combine the platform technology with protein A fragments for functionalization for antibodies.…”

“…[12][13][14][15] To date PVX has been used for epitope presentation approaches in vaccine development; [9,16] chimeric PVX particles have also been combined with enzymes for the fabrication of novel biocatalysts, [17] and PVX is undergoing development as a novel carrier for oncological imaging and therapeutic intervention. [12][13][14][15] To extend the application of PVX, we set out to combine the platform technology with protein A fragments for functionalization for antibodies. The potential application of such antibody-functionalized filaments is envisioned in medical imaging or drug delivery when combined with contrast agents and or toxic payloads as well as in diagnostics; the latter was investigated in the present study.…”