Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles (NP)-embedded silica nanoshuttles (MGNSs) with nanopores on their surface. Fluorescently labeled Doxorubicin (DOX), a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P(NIPAM-co-MAA) to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in: (a) a glass capillary tube to simulate their delivery via blood vessels; and (b) porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood–brain barrier (BBB). The viscoelastic properties of hydrogels were examined by atomic force microscopy (AFM). Cellular uptake of DOX-loaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells (iPSCs) as well as epithelial HeLa cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells’ viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and epithelial cells even though the drug release efficiency was higher in neurons. Therefore, development of smart nanoshuttles have significant translational potential for controlled delivery of theranostics’ payloads and precisely guided transport in specified tissues and organs (for example, bone, cartilage, tendon, bone marrow, heart, lung, liver, kidney, and brain) for highly efficient personalized medicine applications.

Hybrid nanocarriers with multifunctional properties have wide therapeutic and diagnostic applications. We have constructed hollow silica nanogolf balls (HGBs) and gold-embedded hollow silica nanogolf balls (Au@SiO HGBs) using the layer-by-layer approach on a symmetric polystyrene (PS) Janus template; the template consists of smaller PS spheres attached to an oppositely charged large PS core. ζ Potential measurement supports the electric force-based template-assisted synthesis mechanism. Electron microscopy, UV-vis, and near-infrared (NIR) spectroscopy show that HGBs or Au@SiO HGBs are composed of a porous silica shell with an optional dense layer of gold nanoparticles embedded in the silica shell. To visualize their cellular uptake and imaging potential, Au@SiO HGBs were loaded with quantum dots (QDs). Confocal fluorescent microscopy and atomic force microscopy imaging show reliable endocytosis of QD-loaded Au@SiO HGBs in adherent HeLa cells and circulating red blood cells (RBCs). Surface-enhanced Raman spectroscopy of Au@SiO HGBs in RBC cells show enhanced intensity of the Raman signal specific to the RBCs' membrane specific spectral markers. Au@SiO HGBs show localized surface plasmon resonance and heat-induced HeLa cell death in the NIR range. These hybrid golf ball nanocarriers would have broad applications in personalized nanomedicine ranging from in vivo imaging to photothermal therapy.

The formation of this ''ready state'' is orders of magnitude slower than the folding process itself under standard folding conditions. The actual folding step, however, is a unimolecular reaction, i.e., its rate is independent of the overall concentration. These concepts are the basis for a theory that predicts that origami yield will decrease exponentially with the number of folds (e.g., with the size of the origami template). We will discuss this theory and related results on kinetics and fidelity. 164-PlatMeasuring the Conformation of Single Stranded DNA using a DNA Measuring the mechanical properties of single-stranded DNA (ssDNA) is a challenge. Here we describe an innovative method for studying the biophysical properties of ssDNA based on DNA origami. We synthesized a DNA origami structure that consists of two rigid rods with an ssDNA segment between them and image it with atomic force microscopy. The rigid rods provide a means for the exact identification of the ssDNA ends and we measure the end-to-end distance of the ssDNA and analyze it in various ways. By fitting the measured distribution to the ideal chain polymer model, we measured an effective persistence length of 1.98 nm with a standard deviation of 0.72 nm. It also provides information on the conformation and the loops-formation along the ssDNA. It allows to compare the data to previously-published models on the loop formation of RNA and ssDNA structures.This method can be used for measuring stem loops, for determining the effect of repetitive nucleotide sequences and environmental conditions on the mechanical properties of ssDNA, and the effect of interacting proteins with ssDNA.