An Aptamer-Modified DNA Tetrahedron-Based Nanogel for Combined Chemo/Gene Therapy of Multidrug-Resistant Tumors.

DNA-based nanogels have attracted much attention in the biomedical research field. Herein, we report a universal strategy for the fabrication of an aptamer-modified DNA tetrahedron (TET)-based nanogel for combined chemo/gene therapy of multidrug-resistant tumors. In our design, terminal extended antisense oligonucleotides (ASOs) are employed as the linker to co-assemble with two kinds of three-vertex extended TETs for the efficient construction of the DNA-based nanogel. With the incorporation of an active cell-targeting group (aptamer in one vertex of TET) and a controlled-release element (disulfide bridges in the terminals of ASOs), the functional DNA-based nanogel can achieve targeted cellular internalization and stimuli-responsive release of embedded ASOs. After loading with the chemodrug (doxorubicin (DOX), an intercalator of double-stranded DNA), the multifunctional DOX/Nanogel elicits efficient chemo/gene therapy of human MCF-7 breast tumor cells with DOX resistance (MCF-7R). This aptamer-modified DNA tetrahedron-based nanogel provides another strategy for intelligent drug delivery and combined tumor therapy.

Microfluidic Synthesis of Hybrid Nanoparticles with Controlled Lipid Layers: Understanding Flexibility-Regulated Cell-Nanoparticle Interaction.

The functionalized lipid shell of hybrid nanoparticles plays an important role for improving their biocompatibility and in vivo stability. Yet few efforts have been made to critically examine the shell structure of nanoparticles and its effect on cell-particle interaction. Here we develop a microfluidic chip allowing for the synthesis of structurally well-defined lipid-polymer nanoparticles of the same sizes, but covered with either lipid-monolayer-shell (MPs, monolayer nanoparticles) or lipid-bilayer-shell (BPs, bilayer nanoparticles). Atomic force microscope and atomistic simulations reveal that MPs have a lower flexibility than BPs, resulting in a more efficient cellular uptake and thus anticancer effect than BPs do. This flexibility-regulated cell-particle interaction may have important implications for designing drug nanocarriers.

Tunable rigidity of (polymeric core)-(lipid shell) nanoparticles for regulated cellular uptake.

Core-shell nanoparticles (NPs) with lipid shells and varying water content and rigidity but with the same chemical composition, size, and surface properties are assembled using a microfluidic platform. Rigidity can dramatically alter the cellular uptake efficiency, with more-rigid NPs able to pass more easily through cell membranes. The mechanism accounting for this rigidity-dependent cellular uptake is revealed through atomistic-level simulations.

DNA-based self-assembly for functional nanomaterials.

The unprecedented development of DNA nanotechnology has caused DNA self-assembly to attract close attention in many disciplines. In this research news article, the employment of DNA self-assembly in the fields of materials science and nanotechnology is described. DNA self-assembly can be used to prepare bulk-scale hydrogels and 3D macroscopic crystals with nanoscale internal structures, to induce the crystallization of nanoparticles, to template the fabrication of organic conductive nanomaterials, and to act as drug delivery vehicles for therapeutic agents. The properties and functions are fully tunable because of the designability and specificity of DNA assembly. Moreover, because of the intrinsic dynamics, DNA self-assembly can act as a program switch and can efficiently control stimuli responsiveness. We highlight the power of DNA self-assembly in the preparation and function regulation of materials, aiming to motivate future multidisciplinary and interdisciplinary research. Finally, we describe some of the challenges currently faced by DNA assembly that may affect the functional evolution of such materials, and we provide our insights into the future directions of several DNA self-assembly-based nanomaterials.