Yashao Chen

Hydrogel-based microneedles (MNs) have gained significant attention as an advanced transdermal drug delivery platform, offering enhanced bioavailability and promising applications in precision medicine. However, their clinical translation is still hindered by several challenges, most notably insufficient mechanical strength and a lack of precise control over drug release kinetics. Herein, we developed a pH-responsive hydrogel microneedle (MN) system based on natural chitosan (CS) and hyaluronic acid (HA) as the hydrogel matrix. Benzaldehyde terminated F127 triblock copolymers (BAF127) loaded with adapalene (ADP) were incorporated as multifunctional crosslinkers, while β-glycerophosphate (GP) was introduced to modulate the hydrogen-bonding and electrostatic interactions between CS and HA. Under simulated inflammatory conditions (pH 5.5), the MNs exhibited a pH-responsive drug release profile, achieving a cumulative ADP release rate of 94.0% within 10 h. Furthermore, the MNs demonstrated rapid separation of the needle tips from the backing plate within 120 min post-insertion, enhancing transdermal delivery efficiency and skin compatibility. This study presents a robust, pH-responsive hydrogel MN platform that integrates superior mechanical strength with controllable drug release. This work provides a new strategy and technical foundation for the design and clinical translation of high-performance transdermal drug delivery systems.

Magnesium alloys (MgAs) are promising orthopedic implant materials but degrade rapidly in physiological environments, leading to mechanical instability and infection-related complications. Therefore, surface engineering is essential to improve their clinical performance. In this study, a multifunctional MgA surface was fabricated by integrating hydrothermal processing, near-infrared (NIR) photothermal therapy, mussel-inspired adhesion, and photomask-based patterning. Mg(OH)2 nanosheets were first deposited onto the MgA surface via hydrothermal treatment to improve corrosion resistance. Subsequently, polydopamine (PDA) nanoparticles were introduced onto the MgA-Mg(OH)2 substrate, yielding the MgA-Mg(OH)2-PDA (MOD) with photothermal conversion capability. Finally, hydrogel micro-patterns of varying sizes, composed of gelatin methacrylate (PGelMA), polyethylene glycol diacrylate (PEGDA), and the antimicrobial agent naringenin (NG), were fabricated on the MOD surface using a photomask method. Compared with pristine MgA, the hydrogel micro-patterned MOD-PGelMA/PEGDA/NG surface exhibited significantly enhanced corrosion resistance. Notably, the MOD-5 μm sample showed a 113.5-fold increase in polarization resistance (Rp), an approximately three-orders of magnitude reduction in current density (Icorr), and nearly 80% suppression of hydrogen evolution after 21 days of immersion. Furthermore, antifouling behavior, antimicrobial activity, hemolysis rate, and cytocompatibility progressively improved with decreasing hydrogel micro-pattern size. Under NIR irradiation, the MOD-5 μm surface exhibited a synergistic antibacterial effect through the combined photothermal effect of PDA and sustained release of NG, achieving 100% bactericidal efficiency against both E. coli and S. aureus. These results demonstrate the potential of this multifunctional surface engineering strategy for advancing MgA-based orthopedic implants by simultaneously improving corrosion resistance, biocompatibility, and on-demand antibacterial performance.

DNA-metal complexes represent a growing class of artificial metalloenzymes for enantioselective catalysis. Unlike protein pockets, the structural tunability of DNA scaffolds, such as the G-quadruplex, enables dynamic control over enantioselectivity. However, these catalysts often exhibit low catalytic efficiency and limited enantioselectivity switching, underscoring a high demand for rational design strategies to advance this field. Capitalizing on the programmable cytosine-cytosine base pairing in i-motif DNA (imDNA), we develop a tetrad-capping strategy to construct a copper(II) hybrid catalyst (imDNA(H⁺)/Cu²⁺) featuring hemiprotonated cytosine-cytosine base pairs (C-H⁺-C). This catalyst achieves quantitative conversions and up to 98% enantiomeric excess (ee) in Friedel-Crafts reactions. Remarkably, Ag⁺ ions reconfigure imDNA(H⁺) into a distinct imDNA(Ag⁺) conformation, realizing inversion of enantioselectivity (up to -93% ee) with the 4,4'-dimethyl-2,2'-bipyridine copper(II) complex (Cu²⁺(dmbpy)). The chiral inversion originates from distinct H⁺- and Ag⁺-regulated i-motif topologies. Comprehensive spectroscopic, electrophoretic, and thermodynamic analyses reveal that imDNA(Ag⁺) adopts an antiparallel strand orientation stabilized by four C-Ag⁺-C and two G-Ag⁺-G base pairs, in contrast to the capped imDNA(H⁺). The plausible binding sites of catalytic copper(II) species are proposed through binding assays and mutagenesis, where three Cu²⁺ ions are located within three loop regions of imDNA(H⁺), and two Cu²⁺(dmbpy) complexes might primarily interact with imDNA(Ag⁺) via end-stacking. This work establishes a general paradigm for designing tunable DNA hybrid catalysts via programmable base pairing, opening avenues for diverse enantioselective transformations.

Owing to its intrinsic chirality, programmability and structural diversity, DNA functions as an effective chiral ligand for asymmetric catalysis in water. DNA hybrid catalysts are constructed by anchoring metal species into DNA scaffolds through covalent or noncovalent strategies. These DNA-based catalytic systems exhibit potent reactivity and high enantioselectivity in various C–C, C–N, C–O, and C–F bond formation reactions in aqueous media. Importantly, their catalytic activity and product stereochemistry can be precisely directed by modulating DNA sequences, tertiary structures, metal species, and host-guest interaction. This review highlights recent advances in DNA-mediated asymmetric catalysis and discusses future prospects toward tailored stereocontrol under aqueous conditions.

In recent years, sunscreens' adverse impacts on the environment and biology have gained wide attention. The improvement of sunscreen safety has become one of the major priorities in skin photoprotection research. It is an effective strategy to develop bionic photoprotective materials by simulating the photoprotective mechanism existing in nature. Inspired by the photoprotective mechanisms of skin and plant leaves, the bionic photoprotective material CS-SA-PDA nanosheet was developed using the free radical grafting method and Michael addition, with natural melanin analogue polydopamine (PDA) nanoparticles and plant sunscreen molecular sinapic acid (SA) as sun protection factors and natural polymer chitosan (CS) as the connecting arm. The results show that CS-SA-PDA can effectively shield UVB and UVA due to the possible synergistic effect between PDA and SA. The introduction of polymer CS significantly improved the photostability of SA and reduced the skin permeability of PDA nanoparticles. The CS-SA-PDA nanosheet can also effectively scavenge photoinduced free radicals. Furthermore, in vivo toxicity and anti-UV evaluations confirm that CS-SA-PDA has no skin irritation and is excellent against skin photodamage, which makes it an ideal skin photoprotective material.

The diverse structures of DNA serve as potent chiral scaffolds for DNA-based asymmetric catalysis, yet in most cases tens to hundreds of nucleotides in DNA hybrid catalysts hinder the deep insight into their structure-activity relationship. Owing to the structural simplicity and design flexibility of nucleotides, nucleotide-based catalysts have been emerging as a promising way to obtain fine structural information and understand the catalytic mechanisms. Herein, we found that a cyclic dinucleotide of cyclic di-AMP (c-di-AMP) and 1,10-phenanthroline copper(II) nitrate (Cu(phen)(NO₃)₂) are assembled to a c-di-AMP-based catalyst (c-di-AMP/Cu(phen)(NO₃)₂), which could fast achieve enantioselective fluorination in water with 90-99% yields and up to 90% enantiomeric excess (ee). The host-guest interaction between c-di-AMP and Cu(phen)(NO₃)₂ has been proposed mainly in a supramolecular interaction mode as evidenced by spectroscopic techniques of ultraviolet-visible, fluorescence, circular dichroism, and nuclear magnetic resonance. Cu(phen)(NO₃)₂ tightly binds to c-di-AMP with a binding constant of 1.7 ± 0.3 × 10⁵ M^-1, and the assembly of c-di-AMP/Cu(phen)(NO₃)₂ shows a modest rate enhancement to carbon-fluorine bond formations as supported by kinetic studies.