Targeting the Skin: The Study of a Bottlebrush Polymer-Antisense Oligonucleotide Conjugate in a Psoriasis Mouse Model.

The investigation of gene regulation therapeutics for the treatment of skin-related diseases is rarely explored in part due to inefficient systemic delivery. In this study, a bottlebrush polymer-antisense oligonucleotide (ASO) conjugate, termed pacDNA, designed to target IL-17 receptor A (IL-17RA), which is involved in psoriasis pathogenesis is presented. Systemic administration of pacDNA led to its accumulation in epidermis, dermis, and hypodermis of mouse skin, reduced IL-17RA gene expression in skin, and significantly reversed the development of imiquimod (IMQ)-induced psoriasis in a mouse model. These findings highlight the potential of the pacDNA as a promising nanoconstruct for systemic oligonucleotide delivery to the skin and for treating psoriasis and other skin-related disorders through systemic administration.

Inhalable Bottlebrush Polymer Bioconjugates as Vectors for Efficient Pulmonary Delivery of Oligonucleotides.

Antisense oligonucleotides hold therapeutic promise for various lung disorders, but their efficacy is limited by suboptimal delivery. To address this challenge, we explored the use of inhaled bottlebrush polymer-DNA conjugates, named pacDNA, as a delivery strategy. Inhaled pacDNA exhibits superior mucus penetration, achieving a uniform and sustained lung distribution in mice. Targeting the 5' splice site of an aberrant enhanced green fluorescence protein (EGFP) pre-mRNA in EGFP-654 mice, inhaled pacDNA more efficiently corrects splicing than a B-peptide conjugate and restores EGFP expression in the lung. Additionally, in an orthotopic NCI-H358 non-small-cell lung tumor mouse model, inhaled pacDNA targeting wild-type KRAS mRNA effectively suppresses KRAS expression and inhibits lung tumor growth, requiring a substantially lower dosage compared to intravenously injected pacDNA. These findings demonstrate the potential of bottlebrush polymer-DNA conjugates as a promising agent for enhanced oligonucleotide therapy in the lung and advancing the treatment landscape for lung disorders.

Plasma-Engineered N-CoOx Nanowire Array as a Bifunctional Electrode for Supercapacitor and Electrocatalysis.

Surface engineering has achieved great success in enhancing the electrochemical activity of Co3O4. However, the previously reported methods always involve high-temperature calcination processes which are prone to induce agglomeration of the nanostructure, leading to the attenuation of performance. In this work, Co3O4 nanowires were successfully modified by a low-temperature NH3/Ar plasma treatment, which simultaneously generated a porous structure and efficient nitrogen doping with no agglomeration. The modified N-CoOx electrode exhibited remarkable performance due to the synergistic effect of the porous structure and nitrogen doping, which provided additional active sites for faradic transitions and improved charge transfer characteristics. The electrode achieved excellent supercapacitive performance with a maximum specific capacitance of 2862 mF/cm2 and superior cycling retention. Furthermore, the assembled asymmetric supercapacitor (N-CoOx//AC) device exhibited an extended potential window of 1.5 V, a maximum specific energy of 80.5 Wh/kg, and a maximum specific power of 25.4 kW/kg with 91% capacity retention after 5000 charge-discharge cycles. Moreover, boosted hydrogen evolution reaction performance was also confirmed by the low overpotential (126 mV) and long-term stability. This work enlightens prospective research on the plasma-enhanced surface engineering strategies.