title: 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.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, 10900 Euclid Ave., Cleveland, OH 44106, USA. nicole.steinmetz@case.edu.
authors.forename: Duc H T
authors.identifier: http://orcid.org/0000-0001-5611-2595
authors.initials: DH
authors.lastname: Le
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, 10900 Euclid Ave., Cleveland, OH 44106, USA. nicole.steinmetz@case.edu.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, 10900 Euclid Ave., Cleveland, OH 44106, USA. nicole.steinmetz@case.edu.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Shukla
authors.affiliation: Department of Molecular Biotechnology, RWTH-Aachen University, 52064 Aachen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Commandeur
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, 10900 Euclid Ave., Cleveland, OH 44106, USA. nicole.steinmetz@case.edu and Department of Radiology, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA and Department of Materials Science and Engineering, Case Western Reserve University School of Engineering, 10900 Euclid Ave., Cleveland, OH 44106, USA and Department of Macromolecular Science and Engineering, Case Western Reserve University School of Engineering, 10900 Euclid Ave., Cleveland, OH 44106, USA and Division of General Medical Sciences-Oncology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D017863:Potexvirus; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin