P-14

Aptamer-dox conjugates as novel platform for targeted drug deliveryand imagingBagalkot V, C. Farokhzad O, Langer R, Jon S, Gwangju Institute of Scienceand Technology, Gwangju, Korea

For the treatment of cancer, active targeting of drugs is widely used as iteliminates undesirable toxic side effects of most reported anticancer drugsand achieves effective therapy. In the present study we explore the feasibilityof this approach through the use of A10 RNA aptamer as targeting ligandswith high specificity and affinity for PSMA (prostate specific membraneantigen) a prostate specific cancer biomarker. A novel strategy for targeteddrug delivery to cancer cells is reported via formation of a physical conjugatebetween doxorubicin (Dox) and the A10 RNA aptamer through non covalentintercalation of Dox into double stranded regions of the aptamer requiring nomodification of drug or aptamer. In vitro studies showed differential andefficient uptake of the aptamer-Dox physical conjugate into the PSMAexpressing prostate cancer LNCaP cells, and subsequent intracellular releaseof Dox. The data demonstrates a near equipotent cytotoxicity of the aptamer-Dox physical conjugate to the LNCaP cells as compared to the free Dox.Thetargeted cytotoxicity of this system may improve the safety and efficacyprofile of Dox and other intercalating class of drugs. With further intentiontowards developing multifunctional nanoparticles that bear targeting,imaging and therapeutic functions enabling early detection and treatmentof cancer, we report a FRET based nanoprobe comprising of quantum dot(QD) conjugated to aptamer that can load Dox by intercalation. FREToccursbetween Dox and QD, the fluorescence of QD and Dox can be turned offthrough loading of Dox to QD - aptamer conjugate and turned on throughsubsequent release of Dox from the QD - aptamer conjugate. The aptamerwas conjugated to surface of quantum dot and Dox was loaded onto aptamerby non covalent intercalation, resulting in a FRET based nanoprobe forcancer imaging and therapy. The QD-aptamer-Dox conjugate couldefficiently bind to the PSMA expressing prostrate cancer LNCaP cells andrelease Dox with time. This system has the potential to monitor drug releasein a tumor environment.

doi:10.1016/j.nano.2007.10.070

P-15

Thermally cross-linked superparamagnetic iron oxide nanoparticles(TCL-SPION) as a dual cancer imaging probeLee H, Yu MK, Park S, Min JJ, Jeong YY, Jon S, Gwangju Institute ofScience and Technology, Gwangju, Korea

We report the fabrication and characterization of thermally crosslinkedsuperparamagnetic iron oxide nanoparticles (TCL-SPION) and theirapplication to the dual imaging of cancer in vivo. Unlike dextran-coatedcrosslinked iron oxide nanoparticles, which are prepared by a chemicalcrosslinking method, TCL-SPION are prepared by a simple thermalcrosslinking method using a Si-OH-containing copolymer. The copolymer,poly (3-(trimethoxysilyl) propyl methacrylate-r-PEG methyl ether metha-crylate-r-N-acryloxysuccinimide), was synthesized by radical polymerizationand used as a coating material for as-synthesized magnetite (Fe3O4) SPION.The polymer-coated SPIONwas further heated at 80°C to induce crosslinkingbetween the -Si(OH)3 groups in the polymer chains, which finally generatedTCL-SPION bearing a carboxyl group as a surface functional group. Theparticle size, surface charge, presence of polymer-coating layers, and theextent of thermal crosslinking were characterized by dynamic light scattering,Fourier transform-infrared spectroscopy, and X-ray photoelectron spectro-scopy. The carboxyl TCL-SPION was converted to amine-modified TCL-SPION and then finally to Cy5.5 dye-conjugated TCL-SPION for use in dual(magnetic resonance/optical) in vivo cancer imaging. When the Cy5.5 TCL-SPION was administered to Lewis lung carcinoma tumor allograft mice by

intravenous injection, the tumor was detected in T2-weighted magneticresonance images as a 68% signal drop as well as in optical fluorescenceimages within 4 h, indicating a high level of accumulation of the nanomagnetswithin the tumor site. It is noteworthy that, despite the fact that TCL-SPIONdoes not bear any targeting ligands on its surface, it was highly effective fortumor detection in vivo by dual imaging.

doi:10.1016/j.nano.2007.10.071

P-16

Antibiofouling polymer-coated gold nanoparticles as a contrast agentfor in vivo x-ray computed tomography imagingKim D, Park S, Lee JH, Jeong* YY, Jon S, Gwangju Institute of Science andTechnology, Gwangju, Korea

Current computed tomography (CT) contrast agents such as iodine-basedcompounds have several limitations, including short imaging times due torapid renal clearance, renal toxicity, and vascular permeation. Here, wedescribe a new CT contrast agent based on gold nanoparticles (GNPs) thatovercome these limitations. Because gold has a higher atomic number andX-ray absorption coefficient than iodine, we expected that GNPs can beused as CT contrast agents. We prepared uniform GNPs (~30 nm indiameter) by general reduction of HAuCl4 by boiling with sodium citrate.The resulting GNPs were coated with polyethylene glycol (PEG) to impartantibiofouling properties, which extends their lifetime in the bloodstream.Measurement of the X-ray absorption coefficient in vitro revealed that theattenuation of PEG-coated GNPs is 5.7 times higher than that of the currentiodine-based CT contrast agent, Ultravist. Furthermore, when injectedintravenously into rats, the PEG-coated GNPs had a much longer bloodcirculation time (N4 h) than Ultravist (b10 min). Consequently, CT imagesof rats using PEG-coated GNPs showed a clear delineation of cardiacventricles and great vessels. On the other hand, relatively high levels ofGNPs accumulated in the spleen and liver, which contain phagocytic cells.Intravenous injection of PEG-coated GNPs into hepatoma-bearing miceresulted in a high contrast (~2-fold) between hepatoma and normal livertissue on CT images. These results suggest that PEG-coated GNPs can beuseful as a CT contrast agent for a blood pool and hepatoma imaging.

doi:10.1016/j.nano.2007.10.072

P-17

Increased osteoblast adhesion on nano structured selenium- apromising material for orthopedic applicationsTran P 1, Sarin L 2, Hurt R 2, Webster TJ 3, 1Physics Department, BrownUniversity, Providence, Rhode Island, USA., 2Division of Engineering,Brown University, Providence, Rhode Island, USA., 3Division of Engineer-ing and Department of Orthopedic Surgery, Brown University, Providence,Rhode Island, USA

Metallic bone implants possess numerous problems limiting their efficacy,such as poor osseointegration, stress shielding, and corrosion under in vivoenvironments. In addition, these materials were not originally developed tosimultaneously serve as an orthopedic implant and treat bone cancer (forwhich some patients require an orthopedic implant). The objective of thisstudy was to investigate the potential of selenium as a bone implant materialto prevent bone cancer from re-occurring and support new healthy bonegrowth. For this, selenium (spherical or semispherical shots) was pressedinto compacts and then etched using NaOH to obtain various surfacestructures ranging from the micron, sub micron to nano scales. Elementalselenium was also coated on titanium substrates at different coverage levelsusing selenium salt reduction by glutathione. Through these etching andcoating techniques, biologically-inspired nano surface roughness values

352 Posters / Nanomedicine: Nanotechnology, Biology, and Medicine 3 (2007) 347–355

were created on selenium compacts and selenium coated on titanium tomatch those of natural bone. Increased osteoblast (bone-forming cells)adhesion was observed on the more rough selenium compacts and ontitanium substrates with higher levels of selenium coverage. In this manner,this study suggests a promising future for nanostructured selenium inorthopedic applications involving bone cancer treatment.

doi:10.1016/j.nano.2007.10.073

P-18

Composite nanodevices: development for cancer imaging and therapy(including nanobrachytherapy and nanoSTART)Khan* MK 1, Kariapper MST 1, Lesniak WG 1, Kasturirangan V 1, Nair BM 1,Minc LD 2, Balogh LP 1, 1The NanoBiotechnology Center at Roswell ParkCancer Institute (NBC at RPCI), Department of Radiation Medicine, Elmand Carlton Streets, Buffalo, New York, USA., 2OSU Radiation Center,Oregon State University, Corvallis, Oregon, USA

Composite NanoDevices (CNDs) are an exciting class of hybridnanoparticulate materials with several potential medical uses, such ascancer imaging and therapy. The first component of the nanodevices consistof poly(amidoamine) (PAMAM) dendrimer templates that can be made indiscrete sizes, with multiple surface functionalities, and regulated surfacecharges. The other component consists of inorganic material(s), such asgold (Au) that are topologically trapped in the organic matrix withouthaving covalent bonds between the components. They can be converted totargeted ‘nanodevices’ to deliver anticancer drugs to specific organs andtissues. PAMAMs have already been used as delivery vehicles foroligonucleotides, antisense oligonucleotides, and for the delivery ofchemotherapeutic cancer drugs. For several years we have pioneered theexamination of the effects of simple modifications of compositenanodevices on their interactions with complex biological systems in anattempt to understand the characteristics that govern differential biodis-tribution of these nanodevices in mouse tumor model systems. The aim is todetermine principles that may be applied in the future to predict keycharacteristics of composite nanodevices (and potentially other nanode-vices) that determine their biologic interactions. We have also pioneered thedevelopment an angiogenic tumor microvascular targeted compositenanodevice, partly designed based on the nanodevice biodistribution dataabove, and we will discuss the experiments being carried out to examine theuse of this targeted nanodevices to greatly improve tumor nanomolecularimaging. These composite nanodevices are also being developed for novelforms of radiation therapy, both nanobrachytherapy and a nano-systemictargeted radiation therapy (NanoSTaRT).

doi:10.1016/j.nano.2007.10.074

P-19

Characterization of multifunctional tumor angiogenic microvasculartargeted gold PAMAM composite nanodevicesKhan* MK, Kariapper MST, Kasturirangan V, Nair BM, Eranki A, SeggioMN, Lesniak WG, Balogh LP, The NanoBiotechnology Center at RoswellPark Cancer Institute, Department of Radiation Medicine, Roswell ParkCancer Inst., Buffalo, New York, USA

Various strategies have been used to target cancer for both imaging andtherapy. A particularly exciting approach that we have pioneered involvesthe targeting of tumor angiogenic microvasculature instead of tumor cellsusing gold composite nanodevices (Khan et al. (2005) Technol Cancer ResTreat. 4, 603). The RGD peptide sequence has been shown to target αvβ3

integrin receptors of angiogenic endothelial cells. We have fabricated 5 nmpolyamidoamine (PAMAM) based gold (Au) composite nanodevice with

multiple copies of c(RGDfK) peptide and biotin molecules (Au-cRGD-BT-CND) that binds to the αvβ3 integrin. The nanodevice was characterized byvarious analytical methods including polyacrylamide gel electrophoresis,size exclusion chromatography, potentiometric acid-base titration, opticalspectroscopy, MALDI-TOF and NMR. The integrin binding ability of thedevices was assessed in vitro by binding to αvβ3 integrin coated plates, andthe specificity of binding was examined by competition with free cRGDpeptide. Finally, the specific binding of the targeted composite nanodeviceto stimulated human dermal microvasculature endothelial cells wasassessed using a fluorescein tagged antibody against the biotin presenton the composite nanodevice. These experiments show that the Aucomposite nanodevice has high affinity for αvβ3 integrin receptorsexpressed in tumor angiogenic microvascular endothelial cells. Currentlywe are developing this nanodevice with 198Au, so that it can be used as amultifunctional device to direct the payloads of drugs to angiogenicmicrovasculature while enabling real time imaging and internal radiationto destroy tumor blood supply.

doi:10.1016/j.nano.2007.10.075

P-20

Applications of polypeptide multilayer nanofilms in vitro and in vivoHaynie DT, Artificial Cell Technologies, Inc., New Haven, Connecticut, USA

It is widely acknowledged that a major challenge facing medicine today isthe development of new and more useful approaches for the diagnosis,treatment, and management of diseases and injuries. Predictions are thatnanotechnology and nanoscience can have a huge impact on medicine andhow it is practiced. Amidst continuing speculation, practical applications ofnanotechnology and nanoscience are beginning to be realized. ArtificialCell Technologies, Inc. was formed to commercialize engineered polypep-tide multilayer nanofilms. These nanoscale structures have the potential toadvance understanding of biology and medicine in various ways. Currently,the polypeptide multilayer nanofilm technology platform is beingdeveloped to enhance or enable control over cell behavior in vitro and toenhance biosensor lifetime in vivo. Longer-term applications of theplatform technology interest include the development of artificial cellsand synthetic vaccines. This presentation will discuss general aspects ofpolypeptide multilayer nanofilms and recent results in the areas of in vitrocell and tissue culture and enhancement of biosensor function in vivo. Thecell and tissue culture results are relevant to the production of biologics,high-throughput screening in drug discovery, toxicity testing, medicaldiagnostics, and other areas. The biosensor results are relevant to controlledrelease in local drug delivery and control over foreign body reactions.

doi:10.1016/j.nano.2007.10.076

P-21

Polypeptide Multilayer Nanocoatings for Cell Culture and ImplantDevicesDeRome ME 1, Palath N 1, Dave K 1, Rudra JS 1,2, Bhad S 1,2, Klueh U 3,4,Kreutzer DL 3,4, Haynie DT 1,2,3,4, 1Artificial Cell Technologies, Inc., NewHaven, Connecticut, USA., 2Bionanosystems Engineering Laboratory,National Dendrimer and Nanotechnology Center and Department ofChemistry, Central Michigan University, Mt Pleasant, Michigan, USA.,3Center for Molecular Tissue Engineering, University of Connecticut, Schoolof Medicine, Farmington, Connecticut, USA., 4Department of Surgery,University of Connecticut, School of Medicine, Farmington, Connecticut, USA

Multilayer nanofilms made of polypeptides are potentially useful forregulating cell behavior in vitro (e.g. stem cell cultures) and tissues in vivo(e.g. implantable devices). In the present study we determined whether

353Posters / Nanomedicine: Nanotechnology, Biology, and Medicine 3 (2007) 347–355