title: Tobacco mosaic virus-based protein nanoparticles and nanorods for chemotherapy delivery targeting breast cancer.
abstract: Drug delivery systems are required for drug targeting to avoid adverse effects associated with chemotherapy treatment regimes. Our approach is focused on the study and development of plant virus-based materials as drug delivery systems; specifically, this work focuses on the tobacco mosaic virus (TMV). Native TMV forms a hollow, high aspect-ratio nanotube measuring 300×18nm with a 4nm-wide central channel. Heat-transformation can be applied to TMV yielding spherical nanoparticles (SNPs) measuring ~50nm in size. While bioconjugate chemistries have been established to modify the TMV rod, such methods have not yet been described for the SNP platform. In this work, we probed the reactivity of SNPs toward bioconjugate reactions targeting lysine, glutamine/aspartic acid, and cysteine residues. We demonstrate functionalization of SNPs using these chemistries yielding efficient payload conjugation. In addition to covalent labeling techniques, we developed encapsulation techniques, where the cargo is loaded into the SNP during heat-transition from rod-to-sphere. Finally, we developed TMV and SNP formulations loaded with the chemotherapeutic doxorubicin, and we demonstrate the application of TMV rods and spheres for chemotherapy delivery targeting breast cancer.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bruckman
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Czapar
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.
authors.forename: Allen
authors.initials: A
authors.lastname: VanMeter
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Randolph
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States; Department of Radiology, Case Western Reserve University, Cleveland, OH, United States; Department of Materials Science and Engineering, Case Western Reserve University, Cleveland, OH, United States; Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH, United States. Electronic address: nicole.steinmetz@case.edu.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D036022:Capsid Proteins / Q000737:chemistry*; D002470:Cell Survival; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties; D014027:Tobacco Mosaic Virus / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D036022:Capsid Proteins; D004317:Doxorubicin
keywords: Breast cancer; Drug delivery; Nanoparticles; Nanorods; Tobacco mosaic virus