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In reported experimental studies, DNA/polymer self-assemblies are usually kinetically trapped, leading to the encapsulation and irregular collapse of DNA chains within the resultant assemblies. In striking contrast, eukaryotic cells use tetrasome-to-nucleosome pathways to escape possible kinetic trapping for the formation of well-defined 10 nm chromatin fibers. Here, we report a novel pathway for DNA and amphiphilic diblock copolymer self-assembly inspired by the tetrasome pathway with highly controllable kinetics. The polymer is an A- b-B diblock copolymer with a hydrophilic and noninteractive block A and a hydrophobic and interactive block B. Below the critical water content for the micellization, B blocks wrap the backbone of a DNA chain by weak electrostatic interactions to form a linear DNA/polymer complex. With a gradual increase in the water content, the diblock copolymer unimers in the bulk solution tend to aggregate on the linear DNA/polymer complex, which induces the originally wrapped DNA chain, to change its conformation to wrap around the polymer aggregate, guiding and tailoring the self-assembly. Highly controllable kinetics is achieved via the reduced DNA/polymer electrostatic interactions and the high dynamics of the polymer chains in the system. DNA/polymer self-assembly leads to tailorable and morphologically pure core-shell nanofibers. Compared to the DNA/micelle self-assembly pathway described in our previous study, the present self-assembly pathway exhibits advantages for the fabrication of flexible nanofibers with lengths in micrometers and the potential for unique applications in preparing not only 2D networks at extremely low percolation thresholds but also chemiresistors with large on/off current ratios.

In this work, a novel cube-shaped cationic lipid based on the imidazolium salt of polyhedral oligomeric silsesquioxane (POSS) was complexed with double-stranded DNA. Because of the negative spontaneous curvature of the cationic POSS imidazolium lipid, an inverted hexagonal phase resulted above the melting point of POSS crystals. Depending on the competition between the crystallization of POSS molecules and the negative spontaneous curvature of cationic POSS imidazolium lipids, different self-assembled phase morphologies were obtained. A lamellar phase was obtained when the POSS crystallization was relatively slow. When the POSS crystallization was fast, an inverted hexagonal phase was obtained with POSS lamellar crystals grown in the interstitials of DNA cylinders. On the basis of a circular dichroism study, double-stranded DNA adopted the B-form helical conformation in the inverted hexagonal phase, whereas the helical conformation was largely destroyed in the lamellar phase.

Abstract: Transporting drug-containing nanoparticles into the nucleus of cancer cells through nucleopores and then releasing the drug intranuclearly provide an efficient strategy to overcome the drug resistance mechanisms evolved by cancer cells. However, limited by the diameter of nucleopores, nanoparticles capable of going through nucleopores should be small enough, whereas the nanoparticles with the small size may have short circulation time in blood and low accumulation in solid tumors. We solved this dilemma successfully by preparing kinetically frozen large compound nanoparticles (sized 128 nm) of complex of oligolysine/iridium(III) compound (a potential anticancer drug) that can dissociate into small ones in lysosome environment. The small nanoparticles retain their small size in cytosol after escaping from the lysosomes, so that they can enter the nucleus actively through nucleaopores, with the help of oligolysine segments on the surfaces of nanoparticles acting as the nuclear targeting moieties. It is significant that the nanoparticles can release the contained Ir compound within the nucleus. Further study reveals that the release is triggered by DNA interaction with the nanoparticles, which is responsible for the observation that the release occurs only in the nucleus. We believe that the present study, representing the first example of DNA triggered intranuclear release from nanoparticles, will provide a promising pathway for chemotherapy. [Copyright &y& Elsevier]