The Joint Effect of Individual GMA and Team GMA on Safety Participation.

<p>The Joint Effect of Individual GMA and Team GMA on Safety Participation.</p

Means, standard deviation, and correlations of all variables (N = 312).

<p>Note: *p<.01, **p<.001.</p

Aerobic Transition-Metal-Free Visible-Light Photoredox Indole C‑3 Formylation Reaction

An aerobic visible-light-promoted indole C-3 formylation reaction catalyzed by Rose Bengal has been developed. This transition-metal-free process employs molecular oxygen as the terminal oxidant and uses TMEDA as the one-carbon source through C–N bond cleavage. The reaction is compatible with a variety of functional groups

Means, standard deviation, and Zero-order correlations of all variables (n = 99).

<p><i>Note:</i>^*p<.05, ^**p<.01.</p

Hierarchical multiple regression predicting self-reported safety compliance (n = 99).

<p><i>Note</i>: ^*p<.05, ^**p<.01.</p

Moderating effects of inhibition on the influences of controlled and automatic cognitions on safety behaviors.

<p>Panel A shows the moderating effect of inhibition on the influence of safety compromise on safety compliance. Panel B shows the moderating effect of inhibition on the influence of automatic association on safety compliance. Panel C shows the moderating effect of inhibition on the influence of self-reported safety attitude on safety participation. Panel D shows the moderating effect of inhibition on the influence of automatic association on safety participation.</p

Hierarchical multiple regression predicting self-reported safety participation (n = 99).

<p><i>Note</i>: ^*p<.05, ^**p<.01.</p

Engineering the Aromaticity of Cationic Helical Polypeptides toward “Self-Activated” DNA/siRNA Delivery

The development of potent yet nontoxic membrane-penetrating materials is in high demand for effective intracellular gene delivery. We have recently developed α-helical polypeptides which afford potent membrane activities to facilitate intracellular DNA delivery via both endocytosis and the nonendocytic “pore formation” mechanism. Endocytosis will cause endosomal entrapment of the DNA cargo, while excessive “pore formation” would cause appreciable cytotoxicity. Additionally, helical polypeptides with stiff, rodlike structure suffer from low siRNA binding affinity. To address such critical issues, we herein incorporated various aromatic domains (benzyl, naphthyl, biphenyl, anthryl, and pyrenyl) into the side-chain terminals of guanidine-rich, helical polypeptides, wherein the flat-rigid shape, π-electronic structures of aromatic motifs “self-activated” the membrane-penetrating capabilities of polypeptides to promote intracellular gene delivery. Benzyl (Bn)- and naphthyl (Naph)-modified polypeptides demonstrated the highest DNA uptake level that outperformed the unmodified polypeptide, P2, by ∼4 fold. More importantly, compared with P2, Bn- and Naph-modified polypeptides allowed more DNA cargos to be internalized via the nonendocytic pathway, which significantly bypassed the endosomal entrapment and accordingly enhanced the transfection efficiency by up to 42 fold, outperforming PEI 25k as the commercial reagent by 3–4 orders of magnitude. The aromatic modification also improved the siRNA condensation capability of polypeptides, achieving notably enhanced gene-silencing efficiency against tumor necrosis factor-α to treat acute hepatic inflammation. Furthermore, we revealed that aromaticity-augmented membrane activity was accompanied by comparable or even significantly reduced “pore formation” capability, thus leading to diminished cytotoxicity at high concentrations. This study therefore provides a promising approach to manipulate the membrane activities and penetration mechanisms of polycations, which overcomes the multiple critical barriers preventing effective and safe gene delivery

High Drug Loading and Sub-Quantitative Loading Efficiency of Polymeric Micelles Driven by Donor–Receptor Coordination Interactions

Polymeric micelles are extensively used for the delivery of hydrophobic drugs, which, however, suffer from unsatisfactory drug loading, colloidal uniformity, formulation stability, and drug release. Herein, we demonstrate a convenient strategy to prepare micelles with ultrahigh drug loading via the incorporation of polymer–drug coordination interactions. An amphiphilic copolymer containing pendant phenylboronic acid as electron acceptor unit was synthesized, which afforded donor–acceptor coordination with doxorubicin to obtain micelles with ultrahigh drug loading (∼50%), nearly quantitative loading efficiency (>95%), uniform size, and colloidal stability. Besides, the encapsulated drug can be effectively and selectively released in response to the high reactive oxygen species levels in cancer cells, which potentiated the anticancer efficacy and reduced systemic toxicity. Apart from doxorubicin, the current platform could be extended to other drugs with electron-donating groups (e.g., epirubicin and irinotecan), rendering a simple and robust strategy for enabling high drug loading in polymeric micelles and cancer-specific drug release

Efficient Gene Delivery Mediated by a Helical Polypeptide: Controlling the Membrane Activity via Multivalency and Light-Assisted Photochemical Internalization (PCI)

The development of robust and nontoxic membrane-penetrating materials is highly demanded for nonviral gene delivery. Herein, a photosensitizer (PS)-embedded, star-shaped helical polypeptide was developed, which combines the advantages of multivalency-enhanced intracellular DNA uptake and light-strengthened endosomal escape to enable highly efficient gene delivery with low toxicity. 5,10,15,20-Tetrakis-(4-aminophenyl) porphyrin as a selected PS initiated ring-opening polymerization of <i>N</i>-carboxyanhydride and yielded a star-shaped helical polypeptide after side-chain functionalization with guanidine groups. The star polypeptide afforded a notably higher transfection efficiency and lower cytotoxicity than those of its linear analogue. Light irradiation caused almost complete (∼90%) endosomal release of the DNA cargo via the photochemical internalization (PCI) mechanism and further led to a 6–8-fold increment of the transfection efficiency in HeLa, B16F10, and RAW 264.7 cells, outperforming commercial reagent 25k PEI by up to 3 orders of magnitude. Because the PS and DNA cargoes were compartmentalized distantly in the core and polypeptide layers, respectively, the generated reactive oxygen species caused minimal damage to DNA molecules to preserve their transfection potency. Such multivalency- and PCI-potentiated gene delivery efficiency was also demonstrated in vivo in melanoma-bearing mice. This study thus provides a promising strategy to overcome the multiple membrane barriers against nonviral gene delivery