i‑Motif-Driven Au Nanomachines in Programmed siRNA Delivery for Gene-Silencing and Photothermal Ablation

The present work illustrates unique design, construction and operation of an i-motif-based DNA nanomachine templated on gold nanoparticles (AuNPs), which utilizes pH-responsive dynamic motion of i-motif DNA strands and aggregational behavior of AuNPs to elicit programmed delivery of therapeutic siRNA. The pH-sensitive nucleic acids immobilized on the AuNPs consisted of three functional segments, <i>i.e.</i>, an i-motif DNA, an overhanging linker DNA and a therapeutic siRNA. At neutral pH, the i-motif DNA is hybridized with the overhanging linker DNA segment of the therapeutic siRNA. However, in endosomal acidic pH, the i-motif DNA forms interstrand tetraplex, which could induce cluster formation of AuNPs resulting in endosomal escape of AuNP clusters, and produce a high gene silencing efficiency by releasing siRNA in the cytosol. Furthermore, the cluster formation of AuNPs accelerated photothermal ablation of cells when irradiated with laser. Precise and synchronized biomechanical motion in subcellular microenvironment is realized through judicious integration of pH-responsive behavior of the i-motif DNA and AuNPs, and meticulous designing of DNA

DNA-Functionalized Nanochannels for SNP Detection

We have developed ultrahigh density array of functionalized nanochannels by using a block copolymer having end di-COOH group. This approach provides a facile route for direct functionalization of wall surface of the nanochannels and immobilization site for molecular recognition agents (MRAs). By using overhanging single-stranded DNA as MRAs, the DNA-functionalized nanochannels showed high resolution to detect a single-base mismatch as well as to discriminate single-mismatched sequence at various locations by hybridization preference with MRAs

Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination

Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies

Supplementary Information from Synthetic High-density Lipoprotein Nanodiscs for Personalized Immunotherapy Against Gliomas

Supplementary Table 1 Supplementary Figures 1-4</p

Multicomponent-Loaded Vesosomal Drug Carrier for Controlled and Sustained Compound Release

Liposomes have been extensively adopted in drug delivery systems with clinically approved formulations. However, hurdles remain in terms of loading multiple components and precisely controlling their release. Herein, we report a vesosomal carrier composed of liposomes encapsulated inside the core of another liposome for the controlled and sustained release of multiple contents. The inner liposomes are made of lipids with different compositions and are co-encapsulated with a photosensitizer. Upon induction of reactive oxygen species (ROS), the contents of the liposomes are released, with each type of liposome displaying distinct kinetics due to the variance in lipid peroxidation for differential structural deformation. In vitro experiments demonstrated immediate content release from ROS-vulnerable liposomes, followed by sustained release from ROS-nonvulnerable liposomes. Moreover, the release trigger was validated at the organismal level using Caenorhabditis elegans. This study demonstrates a promising platform for more precisely controlling the release of multiple components

Tumor-Targeting Transferrin Nanoparticles for Systemic Polymerized siRNA Delivery in Tumor-Bearing Mice

Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of anticancer drugs because the TF receptor is overexpressed on the surface of various fast-growing cancer cells. In this article, we report on TF nanoparticles as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically modified with sulfhydryl groups that can build up self-cross-linked siRNA-TF NPs. Self-polymerized 5′-end thiol-modified siRNA (poly siRNA, psi) and thiolated transferrin (tTF) were spontaneously cross-linked to form stable NPs (psi-tTF NPs) under optimized conditions, and they could be reversibly degraded to release functional monomeric siRNA molecules under reductive conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific uptake of the psi-tTF NPs, and the internalized NPs resulted in a downregulation of the target protein in red-fluorescent-protein-expressing melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After systemic administration, the psi-tTF NPs showed marked accumulation at the tumor, leading to successful target-gene silencing in vivo. This psi-tTF NP system provided a safe and effective strategy for in vivo systemic siRNA delivery for cancer therapy