Cell Penetrating Polymers Containing Guanidinium Trigger Apoptosis in Human Hepatocellular Carcinoma Cells unless Conjugated to a Targeting <i>N</i>‑Acetyl-Galactosamine Block

A series of 3-guanidinopropyl methacrylamide (GPMA)-based polymeric gene delivery vehicles were developed via aqueous reversible addition–fragmentation chain transfer (RAFT) polymerization. The polymers have been evaluated for their cellular internalization ability, transfection efficiency, and cytotoxicity. Two homopolymers: P­(GPMA₂₀), P­(GPMA₃₄), were synthesized to study the effect of guanidium polymer length on delivery efficiency and toxicity. In addition, an <i>N</i>-acetyl-d-galactosamine (GalNAc)-based hydrophilic block was incorporated to produce diblock polymers, which provides a neutral hydrophilic block that sterically protects plasmid–polymer complexes (polyplexes) from colloidal aggregation and aids polyplex targeting to hepatocytes via binding to asialoglycoprotein receptors (ASGPRs). Polyplexes formed with P­(GPMA_<i>x</i>) (<i>x</i> = 20, 34) homopolymers were shown to be internalized via both energy-dependent and independent pathways, whereas polyplexes formed with block polymers were internalized through endocytosis. Notably, P­(GPMA_<i>x</i>) polyplexes enter cells very efficiently but are also very toxic to human hepatocellular carcinoma (HepG2) cells and triggered cell apoptosis. In comparison, the presence of a carbohydrate block in the polymer structures reduced the cytotoxicity of the polyplex formulations and increased gene delivery efficiency with HepG2 cells. Transfection efficiency and toxicity studies were also carried out with HEK 293T (human embryonic kidney) cells for comparison. Results showed that polyplexes formed with the P­(GPMA_<i>x</i>) homopolymers exhibit much higher transfection efficiency and lower toxicity with HEK 293T cells. The presence of the carbohydrate block did not further increase transfection efficiency in comparison to the homopolymers with HEK 293T cells, likely due to the lack of ASGPRs on the HEK 293T cell line. This study revealed that although guanidinium-based polymers have high membrane permeability, their application as plasmid delivery vehicles may be limited by their high cytotoxicity to certain cell types. Thus, the use of cell penetrating structures in polyplex formulations should be used with caution and carefully tailored toward individual cell/tissue types

Toward High CO Selectivity and Oxidation Resistance Solid Oxide Electrolysis Cell with High-Entropy Alloy

Ni-based cermet materials still persist as pronounced challenges for electrocatalysts in solid oxide electrolysis cells (SOECs), due to their insufficient CO2 catalytic efficiency and inferior resistance to oxidation. In this paper, a (Fe,Co,Ni,Cu,Mo) quinary high-entropy alloy is explored as an alternative cathode material, offering enhanced performance in the co-electrolysis of H2O and CO2 for renewable syngas production. In comparison to traditional nickel-based cathodes, an assembled SOEC employing the as-designed quinary high-entropy alloy exhibits a remarkable increase in CO2 conversion capacity and significantly enhanced oxidation resistance. In addition, the electrolysis current density increases by 18%, and a stability test for more than 110 h reveals no degradation. Moreover, the stability can be maintained for up to 40 h even without any protective gas. Morphological and spectroscopic analyses, coupled with density functional theory (DFT) calculations, elucidate that the high-entropy effect facilitates surface electron redistribution, which in turn contributes to the measurable activity by reducing the energy barrier of CO2 activation. Notably, the superior resistance to oxidation primarily originates from the in situ-formed spinel phase under oxidation conditions. This study demonstrates the satisfying performance of high-entropy alloys as cathode materials in SOEC, validating their high application potential in this field