@article{lockney_guenther_loo_overton_antonelli_clark_hu_luft_lommel_franzen_2011, title={The Red clover necrotic mosaic virus Capsid as a Multifunctional Cell Targeting Plant Viral Nanoparticle}, volume={22}, ISSN={["1520-4812"]}, DOI={10.1021/bc100361z}, abstractNote={Multifunctional nanoparticles hold promise as the next generation of therapeutic delivery and imaging agents. Nanoparticles comprising many types of materials are being tested for this purpose, including plant viral capsids. It has been found that Red clover necrotic mosaic virus (RCNMV) can be loaded with significant amounts of therapeutic molecules with molecular weights of 600 or even greater. Formulation of RCNMV into a plant viral nanoparticle (PVN) involves the loading of cargo and attachment of peptides. In this study, we show that targeting peptides (less than 16 amino acids) can be conjugated to the capsid using the heterobifunctional chemical linker sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC). The uptake of both native RCNMV capsids and peptide-conjugated RCNMV was tested in the HeLa cell line for peptides with and without fluorescent labels. Uptake of RCNMV conjugate with a CD46 targeting peptide was monitored by flow cytometry. When formulated PVNs loaded with doxorubicin and armed with a targeting peptide were delivered to HeLa cells, a cytotoxic effect was observed. The ability to modify RCNMV for specific cell targeting and cargo delivery offers a method for the intracellular delivery of reagents for research assays as well as diagnostic and therapeutic applications.}, number={1}, journal={BIOCONJUGATE CHEMISTRY}, author={Lockney, Dustin M. and Guenther, Richard N. and Loo, Lina and Overton, Wesley and Antonelli, Ray and Clark, Jennifer and Hu, Mei and Luft, Chris and Lommel, Steven A. and Franzen, Stefan}, year={2011}, month={Jan}, pages={67–73} }
 @article{loo_guenther_lommel_franzen_2008, title={Infusion of dye molecules into Red clover necrotic mosaic virus}, ISSN={["1359-7345"]}, DOI={10.1039/b714748a}, abstractNote={The Red clover necrotic mosaic virus capsid is utilized to package and release molecules through reversible depletion and re-addition of divalent cations.}, number={1}, journal={CHEMICAL COMMUNICATIONS}, author={Loo, LiNa and Guenther, Richard H. and Lommel, Steven A. and Franzen, Stefan}, year={2008}, pages={88–90} }
 @article{ryan_overton_speight_oldenburg_loo_robarge_franzen_feldheim_2007, title={Cellular uptake of gold nanoparticles passivated with BSA-SV40 large T antigen conjugates}, volume={79}, ISSN={["1520-6882"]}, DOI={10.1021/ac0715524}, abstractNote={Internalization and subcellular localization in HeLa cells of gold nanoparticles modified with the SV40 large T antigen were quantified using inductively coupled plasma optical emission spectroscopy (ICP-OES). Internalization was monitored as a function of incubation time, temperature, nanoparticle diameter, and large T surface coverage. Increasing the amount of large T peptides per gold nanoparticle complex, by either increasing the coverage at constant nanoparticle diameter or by increasing the nanoparticle diameter at constant large T coverage, resulted in more cellular internalization. In addition, nuclear fractionation was performed to quantify nuclear localization of these complexes as a function of large T coverage. In contrast to our prior qualitative investigations of nuclear localization by video-enhanced color differential interference contrast microscopy (VEC-DIC), ICP-OES was able to detect nanoparticles inside fractionated cell nuclei. Although increasing the large T coverage was found to afford higher cell internalization and nuclear targeting, quantitative evaluation of cytotoxicity revealed that higher large T coverages also resulted in greater cytotoxicity. The ICP-OES and nuclear fractionation techniques reported here are valuable tools that can add important quantitative information to optical and electron imaging methods such as VEC-DIC and transmission electron microscopy regarding the fate of nanoparticles in cells.}, number={23}, journal={ANALYTICAL CHEMISTRY}, author={Ryan, Joseph A. and Overton, K. Wesley and Speight, Molly E. and Oldenburg, Christine M. and Loo, Lina and Robarge, Wayne and Franzen, Stefan and Feldheim, Daniel L.}, year={2007}, month={Dec}, pages={9150–9159} }
 @article{loo_guenther_lommel_franzen_2007, title={Encapsidation of nanoparticles by Red Clover Necrotic Mosaic Virus}, volume={129}, ISSN={["1520-5126"]}, DOI={10.1021/ja071896b}, abstractNote={Icosahedral virus capsids demonstrate a high degree of selectivity in packaging cognate nucleic acid genome components during virion assembly. The 36 nm icosahedral plant virus Red clover necrotic mosaic virus (RCNMV) packages its two genomic ssRNAs via a specific capsid protein (CP) genomic RNA interaction. A 20-nucleotide hairpin structure within the genomic RNA-2 hybridizes with RNA-1 to form a bimolecular complex, which is the origin of assembly (OAS) in RCNMV that selectively recruits and orients CP subunits initiating virion assembly. In this Article, an oligonucleotide mimic of the OAS sequence was attached to Au, CoFe2O4, and CdSe nanoparticles ranging from 3 to 15 nm, followed by addition of RNA-1 to form a synthetic OAS to direct the virion-like assembly by RCNMV CP. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements were consistent with the formation of virus-like particles (VLPs) comparable in size to native RCNMV. Attempts to encapsidate nanoparticles with diameters larger than 17 nm did not result in well-formed viral capsids. These results are consistent with the presence of a 17 nm cavity in native RCNMV. Covalent linkage of the OAS to nanoparticles directs RNA-dependent encapsidation and demonstrates that foreign cargo can be packaged into RCNMV virions. The flexibility of the RCNMV CP to encapsidate different materials, as long as it is within encapsidation constraint, is a critical factor to be considered as a drug delivery and diagnostic vehicle in biomedical applications.}, number={36}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Loo, LiNa and Guenther, Richard H. and Lommel, Steven A. and Franzen, Stefan}, year={2007}, month={Sep}, pages={11111–11117} }
 @article{loo_guenther_basnayake_lommel_franzen_2006, title={Controlled encapsidation of gold nanoparticles by a viral protein shell}, volume={128}, ISSN={["0002-7863"]}, DOI={10.1021/ja057332u}, abstractNote={Icosahedral virus capsids demonstrate a high degree of selectivity in packaging cognate nucleic acid components during assembly. This packaging specificity, when integrated as part of a nanotechnological protocol, has the potential to encapsidate a wide array of foreign materials for delivery of therapeutics or biosensors into target cells. Red clover necrotic mosaic virus (RCNMV) exclusively packages two genomic ssRNAs initiated by a specific protein:RNA interaction between the RCNMV coat protein (CP) and the viral RNA origin of assembly (OAS) element. In the present work, an oligonucleotide mimic of the RCNMV OAS sequences is attached to Au nanoparticles as a recognition signal to initiate the virion-like assembly by RCNMV CP. Covalent linkage of the OAS to Au functions as a trigger for specific encapsidation and demonstrates that foreign cargo can be packaged into RCNMV virions.}, number={14}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Loo, L and Guenther, RH and Basnayake, VR and Lommel, SA and Franzen, S}, year={2006}, month={Apr}, pages={4502–4503} }