Plasmonic Heterostructure Functionalized with a Carbene-Linked Molecular Catalyst for Sustainable and Selective Carbon Dioxide Reduction.

Hybridization of homogeneous catalytic sites with a photoelectrode is an attractive approach to highly selective and tunable photocatalysis using heterogeneous platforms. However, weak and unclear surface chemistry often leads to the dissociation and irregular orientation of catalytic centers, restricting long-term usability with high selectivity. Well-defined and robust ligands that can persist under harsh photocatalytic conditions are essential for the success of hybrid-type photocatalysis. Here, we introduce N-heterocyclic carbene as a durable linker for the immobilization of a Rubpy complex-based CO2 reduction site (cis-dichloro-(4,4'-diphosphonato-Rubpy)(p-cymene) (RuCY)) on a p-type gallium nitride/gold nanoparticle (p-GaN/AuNP) heterostructure. The p-GaN/AuNPs/RuCY photocathode was coupled with a hematite photoanode to drive photoelectrochemical CO2 reduction along with water oxidation. Highly selective CO2 reduction into formates, up to 98.2%, was achieved utilizing plasmonic hot electrons accumulated on AuNPs. The turnover frequency was 1.46 min-1 with a faradic efficiency of 96.8% under visible light illumination (243 mW·cm-2). This work demonstrates that the N-heterocyclic carbene-mediated surface functionalization with homogeneous catalytic sites is a promising approach to increase the sustainability and usability of hybrid catalysts.

Directed Nanoscale Self-Assembly of Natural Photosystems on Nitrogen-Doped Carbon Nanotubes for Solar-Energy Harvesting.

Natural photosystems (PSs) have received much attention as a biological solar energy harvester because of their high quantum efficiency for energy transfer. However, the PSs hybridized with solid electrodes exhibit low light-harvesting efficiencies because of poor interface properties and random orientations of PSs, all of which interfere with efficient charge extraction and transfer. Herein, we report the linker-free, oriented self-assembly of natural PSs with nitrogen-doped carbon nanotubes (NCNTs) via electrostatic interaction. Protonated nitrogen-doped sites on the NCNTs facilitate spontaneous immobilization of the negatively charged stroma side of PSs, which provides a favorable orientation for electron transfer without electrically insulating polymer linkers. The resulting PS/NCNT hybrids exhibit a photocurrent density of 1.25 ± 0.08 µA cm-2, which is much higher than that of PS/CNT hybrids stabilized with polyethylenimine (0.60 ± 0.01 µA cm-2) and sodium dodecyl sulfate (0.14 ± 0.01 µA cm-2), respectively. This work emphasizes the importance of the linker-free assembly of PSs into well-oriented hybrid structures to construct an efficient light-harvesting electrode.

Lipiodol nanoemulsions stabilized with polyglycerol-polycaprolactone block copolymers for theranostic applications.

BACKGROUND: Polyglycerol is an attractive hydrophilic building block of amphiphilic copolymers for biomedical and pharmaceutical applications due to its biocompatibility, facile chemical modification, and anti-fouling activity. Herein we introduce theranostic nanoemulsions incorporating anti-cancer therapeutic and contrast agents using linear polyglycerol-poly(ε-caprolactone) diblock copolymers (PG-b-PCL). Lipiodol is used as a core oil that dissolves paclitaxel and serves as a contrast agent for computer tomography (CT). METHODS: PG-b-PCL is synthesized by three-step processes: polymerization of ethoxyethyl glycerol ether; ring-opening polymerization of ε-caprolactone; and deprotection of the PEEGE block. In vitro cytotoxicity of the polyglycerolated lipiodol nanoemulsions is demonstrated using HeLa ovarian cancer cells. The applicability of the prepared nanoemulsions as a contrast agent for CT imaging is also evaluated using micro-CT. RESULTS: Three compositions of PG-b-PCL with different block lengths are synthesized to prepare nanoemulsions. The polyglycerolated lipiodol nanoemulsions exhibit excellent anti-cancer activities, while placebo nanoemulsions have no significant cytotoxicity under the same condition. Micro-CT imaging of the nanoemulsions confirms the ability of nanoemulsions as a contrast agent. CONCLUSIONS: This study suggests that PG-b-PCL is a promising polymeric emulsifier for effective stabilization and surface functionalization of drug delivery nanocarriers for therapeutic and imaging agents.

Polyglycerolated nanocarriers with increased ligand multivalency for enhanced in vivo therapeutic efficacy of paclitaxel.

Despite the excellent biocompatibility and antifouling effect of poly(ethylene glycol) (PEG), the high steric hindrance, limited chemical functionality, and low ligand multivalency of PEGylated nanocarriers often lead to inefficient cell targeting and intracellular trafficking. Hence, a new structure of hydrophilic corona allowing a higher ligand density without loss of excellent biocompatibility is highly desirable. Here we introduce tumor-targeted polyglycerolated (PGylated) nanocarriers that dramatically enhance the in vivo therapeutic efficacy of incorporated paclitaxel simply by increasing the surface density of hydrophobic tumor-targeting ligands. Linear polyglycerol-poly (ε-caprolactone) block copolymer (PG-b-PCL) is used to prepare PGylated lipiodol nanoemulsions, where PG serves as a corona conjugated with a large number of folic acid (FA) for efficient tumor targeting. Unlike FA-PEGylated nanoemulsions, FA-PGylated nanoemulsions can display a larger number of FA without structural destabilization. This property enables excellent anti-cancer activities and effective tumor regression in a cervical cancer xenograft murine model at a cumulative drug dose of ∼5 mg kg-1, which is about four fold smaller than that of commercial Taxol formulation. This study highlights the importance of surface chemistry of nanocarriers that enable multivalent ligand functionalization and high tolerance to the conjugation of hydrophobic ligands, which make PG as a very effective hydrophilic corona for in vivo drug delivery.

Importance of crystallinity of anchoring block of semi-solid amphiphilic triblock copolymers in stabilization of silicone nanoemulsions.

Polymer emulsifiers solidified at the interface between oil and water can provide exceptional dispersion stability to emulsions due to the formation of unique semi-solid interphase. Our recent works showed that the structural stability of paraffin-in-water emulsions highly depends on the oil wettability of hydrophobic block of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-b-PCL). Here we investigate the effects of the crystallinity of hydrophobic block of triblock copolymer-based emulsifiers, PCLL-b-PEG-b-PCLL, on the colloidal properties of silicone oil-in-water nanoemulsions. The increased ratio of l-lactide to ε-caprolactone decreases the crystallinity of the hydrophobic block, which in turn reduces the droplet size of silicone oil nanoemulsions due to the increased chain mobility at the interface. All of the prepared nanoemulsions are very stable for a month at 37°C. However, the exposure to repeated freeze-thaw cycles quickly destabilizes the nanoemulsions prepared using the polymer with the reduced crystallinity. This work demonstrates that the anchoring chain crystallization in the semi-solid interphase is critically important for the structural robustness of nanoemulsions under harsh physical stresses.

Stable nanoemulsions prepared via interfacial solidification of amphiphilic polyether-polyester block copolymers.

Oil-in-water (O/W) emulsions are generally stabilized by water-soluble surfactants, which anchor to the surface of oil droplets dispersed in an aqueous solution. Our recent work introduced a new approach to stabilize nanoemulsions through the formation of a semi-solid interphase at the O/W interface using a water-insoluble amphiphilic block copolymer, methoxy poly(ethylene glycol)-block-poly(ɛ-caprolactone). However, the approach is not applicable to relatively non-polar oils due to the quick precipitation of the hydrophobic PCL block within the oil phase. Here we report on successful stabilization of non-polar liquid paraffin nanoemulsions using an amphiphilic copolymers having a new hydrophobic block comprising ɛ-caprolactone and L-lactide. The new block copolymer was reorganized at the O/W interface of liquid paraffin, generating stable nano-sized emulsions via the formation of a robust semi-solid polymeric barrier. The prepared nanoemulsions show excellent dispersion stability even under a high level of mechanical stresses during freeze/thaw cycles.

Fluorescent phosphoinositide 3-kinase inhibitors suitable for monitoring of intracellular distribution.

The monitoring of the drug behavior and distribution in biological system can provide information whether drug reaches its desired target, and a biological rationale for the design of new therapeutics. We have developed a family of potent fluorescent PI3Kα inhibitors in which part of the fluorophore was engineered to be a pharmacophore capable of inhibiting PI3Kα. These xanthine derivatives are characterized by a donor-acceptor molecular structure, and changes in the electronic properties of the two variation points at R(1) and R(2) give rise to notable bathochromic shifts in the λ(em, abs) and increase the value of Φ(F). Further, we illustrated the use of E2 (PI3Kα/IC(50)=0.068 µM, T47D cell viability: IC(50)=0.9 µM) to block cancer cell proliferation and to monitor its subcellular localization by fluorescence microscopy.

Development of new fluorescent xanthines as kinase inhibitors.

An efficient and versatile synthetic approach for the preparation of highly substituted xanthine derivatives has been developed by a combination of direct N7- and C8-arylation. With this method, diverse xanthine analogues were prepared and potent kinase inhibitors could be identified. For example, compound 8a inhibits PI3Ks and proliferation in T47D tumor cells. In addition, these xanthine-based kinase inhibitors exhibited significant fluorescence emission in a concentration-dependent response.