Feasibility Study of Dendrimer-Based TTR-CRISPR pDNA Polyplex for Ocular Amyloidosis in Vitro.

Hereditary amyloidgenic transthyretin (ATTR) amyloidosis is caused by a genetic point-mutated transthyretin such as TTR Val30Met (TTR V30M), since it forms protein aggregates called amyloid resulting in the tissue accumulation and functional disorders. In particular, ATTR produced by retinal pigment epithelial cells often causes ATTR ocular amyloidosis, which elicits deterioration of ocular function and ultimately blindness. Therefore, development of novel therapeutic agents is urgently needed.

Stabilization and Movable Ligand-Modification by Folate-Appended Polyrotaxanes for Systemic Delivery of siRNA Polyplex.

To achieve a systemic targeted delivery of siRNA using polymeric carriers, there is a dilemma between ligand modification and stabilization of the polyplex. Namely, ligand modification often leads to destabilization of the polyplex in the blood circulation. In fact, we previously developed cyclodextrin (CD)/polyamidoamine dendrimer conjugates (CDE) as siRNA carriers, and the interaction of CDE/siRNA was decreased by the conjugation with folate-polyethylene glycol, leading to the destabilization.

Multifunctional Therapeutic Cyclodextrin-Appended Dendrimer Complex for Treatment of Systemic and Localized Amyloidosis.

Amyloidosis pathologically proceeds via production of amyloidogenic proteins by organs, formation of protein aggregates through structural changes, and their deposition on tissues. A growing body of evidence demonstrates that amyloidosis generally develops through three critical pathological steps: (1) production of amyloid precursor proteins, (2) amyloid formation, and (3) amyloid deposition. However, no clinically effective therapy that is capable of targeting each pathological step of amyloidosis independently is currently available.

Genome Editing in a Wide Area of the Brain Using Dendrimer-Based Ternary Polyplexes of Cas9 Ribonucleoprotein.

A preassembled Cas9/single-guide RNA complex (Cas9 ribonucleoprotein; Cas9 RNP) induces genome editing efficiently, with small off-target effects compared with the conventional techniques, such as plasmid DNA and mRNA systems. However, penetration of Cas9 RNP through the cell membrane is low. In particular, the incorporation of Cas9 RNP into neurons and the brain is challenging.

Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis.

Amyloidogenic transthyretin (ATTR) amyloidosis is caused by a formation of ATTR amyloid fibrils. Because ATTR misfolding triggers the formation of aggregates and amyloid fibrils, which are considered to deposit on the tissues, novel clinically effective therapeutic strategies targeted to those processes are urgently needed. In this study, to discover a new drug candidate for ATTR amyloidosis therapy, we focused on polyamidoamine dendrimer (dendrimer), a 3D-structural nanomaterial, which has a branched cationic polymer repeating polyamidoamine units.

pH-responsive polymeric micelles with core-shell-corona architectures as intracellular anti-cancer drug carriers.

Polymeric micelles with core-shell-corona nanoarchitecture were designed for intracellular therapeutic anti-cancer drug carriers. Poly(styrene--acrylic acid--ethylene glycol) (PS--PAA--PEG) asymmetric triblock copolymer underwent self-assembly in aqueous solution to form spherical micelles with hydrophobic PS core, anionic PAA shell and hydrophilic PEG corona. The anti-cancer drug (doxorubicin, DOX) was successfully incorporated into the polymeric micelles.

Preparation and characterization of polyion complex micelles with phosphobetaine shells.

A pair of oppositely charged diblock copolymers, poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-poly((3-(methacryloylamino)propyl)trimethylammonium chloride) (PMPC-b-PMAPTAC) and poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-poly(sodium 2-(acrylamido)-2-methylpropanesulfonate) (PMPC-b-PAMPS), was prepared via reversible addition-fragmentation chain transfer radical polymerization using a PMPC-based macro chain transfer agent. The pendant phosphorylcholine group in the hydrophilic PMPC block has anionic phosphate and cationic quaternary amino groups, which are neutralized within the pendant group. Therefore, the mixing of aqueous solutions of PMPC-b-PMAPTAC and PMPC-b-PAMPS leads to the spontaneous formation of simple core-shell spherical polyion complex (PIC) micelles comprising of a segregated PIC core and PMPC shells.

Inorganic-organic hybrid nanoparticles with biocompatible calcium phosphate thin shells for fluorescence enhancement.

Polymeric micelles consisting of asymmetric triblock copolymers were successfully used for fabrication of robust hybrid nanoparticles with highly biocompatible calcium phosphate shells. The hydrophobic polystyrene core encapsulates hydrophobic fluorescent dyes such as Nile red. The anionic polyacrylic acid provides the site for the mineralization reaction of calcium phosphate.

Multifunctional core-shell-corona-type polymeric micelles for anticancer drug-delivery and imaging.

We have developed core-shell-corona-type polymeric micelles that can integrate multiple functions in one system, including the capability of accommodating hydrophobic dyes into core and hydrophilic drug into the shell, as well as pH-triggered drug-release. The neutral and hydrophilic corona sterically stabilizes the multifunctional polymeric micelles in aqueous solution. The mineralization of calcium phosphate (CaP) on the PAA domain not only enhances the diagnostic efficacy of organic dyes, but also works as a diffusion barrier for the controlled release.

La2O3 hollow nanospheres for high performance lithium-ion rechargeable batteries.

An efficient and simple protocol for synthesis of novel La(2)O(3) hollow nanospheres of size about 30 ± 2 nm using polymeric micelles is reported. The La(2)O(3) hollow nanospheres exhibit high charge capacity and cycling performance in lithium-ion rechargeable batteries (LIBs), which was scrutinized for the first time among the rare-earth oxides.

Novel LaBO3 hollow nanospheres of size 34±2 nm templated by polymeric micelles.

Novel lanthanum borate (LaBO(3)) hollow nanospheres of size 34±2 nm have been reported for the first time by soft-template self-assembly process. Poly(styrene-b-acrylic acid-b-ethylene oxide) (PS-PAA-PEO) micelle with core-shell-corona architecture serves as an efficient soft template for fabrication of LaBO(3) hollow particles using sodium borohydride (NaBH(4)) and LaCl(3)⋅7H(2)O as the precursors. In this template, the PS block (core) acts as a template of the void space of hollow particle, the anionic PAA block (shell) serves as reaction field for metal ion interactions, and the PEO block (corona) stabilizes the polymer/lanthana composite particles.

Periodic organosilica hollow nanospheres as anode materials for lithium ion rechargeable batteries.

Polymeric micelles with core-shell-corona architecture have been found to be the efficient colloidal templates for synthesis of periodic organosilica hollow nanospheres over a broad pH range from acidic to alkaline media. In alkaline medium, poly (styrene-b-[3-(methacryloylamino)propyl] trimethylammonium chloride-b-ethylene oxide) (PS-PMAPTAC-PEO) micelles yield benzene-silica hollow nanospheres with molecular scale periodicity of benzene groups in the shell domain of hollow particles. Whereas, an acidic medium (pH 4) produces diverse hollow particles with benzene, ethylene, and a mixture of ethylene and dipropyldisulfide bridging functionalities using poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) micelles.

Novel titania hollow nanospheres of size 28 ± 1 nm using soft-templates and their application for lithium-ion rechargeable batteries.

We report a novel protocol to prepare titania hollow nanospheres of size about 28 ± 1 nm with micelles of asymmetric triblock copolymers. The hollow particles exhibit unique electrochemical properties in lithium ion rechargeable batteries such as high capacity, very low irreversible capacity loss, and high cycling performance.