Potato virus X, a filamentous plant viral nanoparticle for doxorubicin delivery in cancer therapy

Abstract

Plant viral nanoparticles (VNPs) are a novel class of nanocarriers with implications for drug delivery in cancer therapy. VNPs are characterized by their highly symmetrical nanoscale structures. Furthermore, plant VNPs are biocompatible, biodegradable, and non-infectious in mammals. VNPs provide a proteinaceous platform technology that can be readily engineered to carry contrast agents and therapies using chemical and genetic modifications. Of particular interest are high aspect ratio, elongated filaments such as the ones formed by potato virus X (PVX, measuring 515 × 13 nm). PVX has demonstrated enhanced tumor homing and penetration properties compared to spherical counterparts. Here, we sought to investigate the potential of PVX as a drug carrier delivering doxorubicin (DOX), a commonly used cancer chemotherapy. We synthesized therapeutic PVX nanoparticles using a simple in-solution mixing protocol; after 5 days of mixing of DOX and PVX and ultra-centrifugal purification, ~1000 DOX per PVX were stably associated with the carrier, most likely based on hydrophobic interaction. Efficacy and drug activity of PVX-DOX were confirmed using a panel of cancer cell lines including ovarian cancer, breast cancer, and cervical cancer. Lastly, we demonstrated treatment of athymic mice bearing human MDA-MB-231 breast cancer xenografts: PVX-DOX treatment resulted in reduced tumor growth in this model. Our results open the door for further development of PVX and other high aspect ratio plant VNPs for applications in cancer therapy.

Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs

“…64,65 We have previously proposed that DOX associates with PVX particles via hydrophobic interactions, specifically involving π – π stacking between the benzene rings of DOX and nonpolar aromatic amino acids such as phenylalanine, tyrosine, and tryptophan. 66 Likewise, DOX can also interact via π – π stacking with other DOX molecules. After Coomassie staining, the PS-PhMV and DOX-PhMV coat proteins appeared as two bands representing the monomer and a dimer, indicating some degree of aggregation (Figure 2A, lanes 4, 6).…”

“…75 We have demonstrated that CPMV, PVX, and TMV achieve the efficient delivery of DOX and targeted cell killing using bioconjugation and encapsulation protocols. 66,76,77 …”

A review on the biosynthesis of metal and metal salt nanoparticles by microbes

“…Le et al investigated the potential of potato virus X nanoparticles for the delivery of doxorubicin drug for cancer treatment. 114 Potato virus X has the capability to synthesize elongated lamentous nanoparticles which exhibits…”

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

“…Similarly, the reversible pore-opening process of the red clover necrotic mosaic virus (RCNMV) capsid allowed loading and release of doxorubicin (as well as other drugs) in a pH- and divalent cation-dependent manner [29]. More recently, we also demonstrated the non-covalent complexation of doxorubicin to high aspect ratio, flexuous potato virus X (PVX); the formulation exhibited enhanced efficacy vs. free drug in a mouse model of triple negative breast cancer [30]. …”