Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
Nanoscale. 2023 Sep 14;15(35):14531-14542. doi: 10.1039/d3nr03231k.
Chronic wounds exhibit over-expression of cell-free deoxyribonucleic acid (cfDNA), leading to a prolonged inflammation and non-healing wounds. Scavenging excessive cfDNA molecules is a promising strategy for chronic wound treatment. Nanoscopic particles act as efficient cfDNA scavengers due to their large surface area, however their efficiency in cfDNA uptake was limited by adsorption solely on the nanoparticle surface. In contrast, nanogels may provide multiple cfDNA binding sites in the nanoparticle interior, however their use for cfDNA scavenging is yet to be explored. Herein, we report cationic nanogels derived from a copolymer of chitosan and poly{2-[(acryloyloxy)ethyl]trimethylammonium chloride} end-grafted to the chitosan backbone as side chains. The nanogels retain their positive charge at the pH and ionic strength of chronic wound exudate, enabling electrostatically driven cfDNA scavenging. The network structure of the nanogels leads to the cfDNA sequestration in the nanogel interior, in addition to surface attachment. A key factor in cfDNA sequestration is the ratio of the pore size of the nanogel-to-cfDNA molecular dimensions. The enhanced cfDNA scavenging efficiency, along with biocompatibility of the nanogels, makes them a promising component of dressings for chronic wound treatment.
慢性创面表现出游离脱氧核糖核酸（cfDNA）的过度表达，导致持续的炎症和不愈合的伤口。清除过多的 cfDNA 分子是治疗慢性创面的一种有前途的策略。由于纳米粒子具有较大的表面积，因此它们作为有效的 cfDNA 清除剂发挥作用，然而，其 cfDNA 摄取效率受到仅在纳米粒子表面吸附的限制。相比之下，纳米凝胶可能在纳米粒子内部提供多个 cfDNA 结合位点，但其用于 cfDNA 清除的用途尚未得到探索。在此，我们报告了一种源自壳聚糖和聚{2-[(丙烯酰氧基)乙基]三甲基氯化铵}的共聚物的阳离子纳米凝胶，其端基接枝在壳聚糖主链上作为侧链。纳米凝胶在慢性创面渗出液的 pH 值和离子强度下保持正电荷，从而能够进行静电驱动的 cfDNA 清除。纳米凝胶的网络结构导致 cfDNA 被隔离在纳米凝胶内部，除了表面附着。cfDNA 隔离的一个关键因素是纳米凝胶的孔径与 cfDNA 分子尺寸的比值。增强的 cfDNA 清除效率以及纳米凝胶的生物相容性使它们成为慢性创面治疗敷料的有前途的组成部分。
