University of Connecticut,
Keywords: Janus base nanotubes, nanopieces, RNA and drug delivery
Summary:Therapeutic delivery into deep tissues with dense extracellular matrix (ECM) has been challenging. For example, cartilage is a major barrier for RNA and drug delivery due to its avascular structure, low cell density and strong negative surface charge. Cartilage ECM is comprised of collagens, proteoglycans, and various other noncollagneous proteins with a spacing of 20nm. Conventional nanoparticles are usually spherical with a diameter larger than 50-60nm (after cargo loading). Therefore, they presented limited success for delivery into cartilage. Here, we developed Janus base nanotubes (JBNTs, self-assembled nanotubes inspired from DNA base pairs) to assemble with therapeutic molecules to form nano-rod delivery vehicles (termed as “Nanopieces”). Nanopieces have a diameter of smaller than 20nm (smallest delivery vehicles after cargo loading) and a length over 50nm. They present a novel breakthrough in deep tissue penetration due to the reduced size and adjustable characteristics to encourage ECM and intracellular penetration. JBNTs are comprised of self-assembled supramolecular structures which are further broken down into DNA base pairs. The hollow channels formed by these nanotubes are ideal for drug loading and the six-member rosette comprised of hydrogen bonding is essential for its low cytotoxicity profile. By controlled assembly between the therapeutic cargos with JBNT solution, long segmented Nanopieces are synthesized. They can be further separated via a regulated sonication process. Nanopieces with formulations were assembled and their material properties were studied using dynamic light scattering (DLS) and Zeta potential measurements. Their morphological characteristics and distributions were analyzed by transmission electron microscopy (TEM) imaging. The delivery abilities of Nanopieces with different formulations were determined in vitro and in vivo. Results of this study provide in-depth characterizations of these Nanopieces along with evaluating their abilities of therapeutic delivery.