@misc{franzen_feldheim_tkachenko_godek_ryan_anderson_2008, title={Nanoparticle delivery vehicle}, volume={7,332,586}, number={2008 Feb. 19}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Franzen, S. and Feldheim, D. L. and Tkachenko, A. G. and Godek, M. L. and Ryan, J. A. and Anderson, M. F.}, year={2008} }
 @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{tkachenko_xie_liu_coleman_ryan_glomm_shipton_franzen_feldheim_2004, title={Cellular trajectories of peptide-modified gold particle complexes: Comparison of nuclear localization signals and peptide transduction domains}, volume={15}, ISSN={["1520-4812"]}, DOI={10.1021/bc034189q}, abstractNote={Gold nanoparticles modified with nuclear localization peptides were synthesized and evaluated for their subcellular distribution in HeLa human cervical epithelium cells, 3T3/NIH murine fibroblastoma cells, and HepG2 human hepatocarcinoma cells. Video-enhanced color differential interference contrast microscopy and transmission electron microscopy indicated that transport of nanoparticles into the cytoplasm and nucleus depends on peptide sequence and cell line. Recently, the ability of certain peptides, called protein transduction domains (PTDs), to transclocate cell and nuclear membranes in a receptor- and temperature-independent manner has been questioned (see for example, Lundberg, M.; Wikstrom, S.; Johansson, M. (2003) Mol. Ther. 8, 143-150). We have evaluated the cellular trajectory of gold nanoparticles carrying the PTD from HIV Tat protein. Our observations were that (1) the conjugates did not enter the nucleus of 3T3/NIH or HepG2 cells, and (2) cellular uptake of Tat PTD peptide-gold nanoparticle conjugates was temperature dependent, suggesting an endosomal pathway of uptake. Gold nanoparticles modified with the adenovirus nuclear localization signal and the integrin binding domain also entered cells via an energy-dependent mechanism, but in contrast to the Tat PTD, these signals triggered nuclear uptake of nanoparticles in HeLa and HepG2 cell lines.}, number={3}, journal={BIOCONJUGATE CHEMISTRY}, author={Tkachenko, AG and Xie, H and Liu, YL and Coleman, D and Ryan, J and Glomm, WR and Shipton, MK and Franzen, S and Feldheim, DL}, year={2004}, pages={482–490} }
 @article{xie_tkachenko_glomm_ryan_brennaman_papanikolas_franzen_feldheim_2003, title={Critical flocculation concentrations, binding isotherms, and ligand exchange properties of peptide-modified gold nanoparticles studied by UV-visible, fluorescence, and time-correlated single photon counting spectroscopies}, volume={75}, ISSN={["0003-2700"]}, DOI={10.1021/ac034578d}, abstractNote={Protocols for modifying gold nanoparticles with peptide-bovine serum albumin (BSA) conjugates are described within. The resulting constructs were characterized using a number of techniques including static fluorescence spectroscopy and time-correlated single photon counting spectroscopy (TCSPC) in order to quantify peptide-BSA binding isotherms, exchange rates, critical flocculation concentrations, and the composition of mixed peptide-BSA monolayers on gold nanoparticles. TCSPC has proven to be a powerful technique for observing the microenvironment of protein-gold nanoparticle conjugates because it can distinguish between surface-bound and solution-phase species without the need for separation steps. Full characterization of the composition and stability of peptide-modified metal nanoparticles is an important step in their use as intracellular delivery vectors and imaging agents.}, number={21}, journal={ANALYTICAL CHEMISTRY}, author={Xie, H and Tkachenko, AG and Glomm, WR and Ryan, JA and Brennaman, MK and Papanikolas, JM and Franzen, S and Feldheim, DL}, year={2003}, month={Nov}, pages={5797–5805} }
 @article{tkachenko_xie_coleman_glomm_ryan_anderson_franzen_feldheim_2003, title={Multifunctional gold nanoparticle-peptide complexes for nuclear targeting}, volume={125}, ISSN={["0002-7863"]}, DOI={10.1021/ja0296935}, abstractNote={The ability of peptide-modified gold nanoparticles to target the nucleus of HepG2 cells was explored. Five peptide/nanoparticle complexes were investigated, particles modified with (1) the nuclear localization signal (NLS) from the SV 40 virus; (2) the adenovirus NLS; (3) the adenovirus receptor-mediated endocytosis (RME) peptide; (4) one long peptide containing the adenovirus RME and NLS; and (5) the adenovirus RME and NLS peptides attached to the nanoparticle as separate pieces. Gold nanoparticles were used because they are easy to identify using video-enhanced color differential interference contrast microscopy, and they are excellent scaffolds from which to build multifunctional nuclear targeting vectors. For example, particles modified solely with NLS peptides were not able to target the nucleus of HepG2 cells from outside the plasma membrane, because they either could not enter the cell or were trapped in endosomes. The combination of NLS/RME particles (4) and (5) did reach the nucleus; however, nuclear targeting was more efficient when the two signals were attached to nanoparticles as separate short pieces versus one long peptide. These studies highlight the challenges associated with nuclear targeting and the potential advantages of designing multifunctional nanostructured materials as tools for intracellular diagnostics and therapeutic delivery.}, number={16}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Tkachenko, AG and Xie, H and Coleman, D and Glomm, W and Ryan, J and Anderson, MF and Franzen, S and Feldheim, DL}, year={2003}, month={Apr}, pages={4700–4701} }