Production of reactive species in alginate hydrogels for cold atmospheric plasma-based therapies
Production of reactive species in alginate hydrogels for cold atmospheric plasma-based therapies
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DOI：
10.1038/s41598-019-52673-w
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发表时间：
2019-11-06
影响因子：
4.6
通讯作者：
Canal, Cristina
中科院分区：
文献类型：
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作者：
Labay, Cedric;Hamouda, Ines;Canal, Cristina
在过去的几年里，基于冷大气等离子体（CAP）的治疗取得了很大的进展。CAP产生活性氧和活性氮（ron），它们可以转移到液体中。这些CAP活性液体显示出与CAP本身相同的生物功效（即杀死癌细胞），为微创治疗打开了大门。然而，由于细胞外液和血液流动，在体内注射液体会导致快速扩散。因此，开发高效的车辆，允许局部限制并将RONS运送到患病部位是一项基本要求。在这项工作中，我们通过比较两种大气压等离子体射流：kINPen和氦针，在一系列等离子体处理条件（时间、气体流量、与样品的距离）下，研究了藻酸盐水凝胶中RONS （H2O2、NO2-、短寿命RONS）的产生。等离子体处理后，水凝胶的物理化学性质保持不变，而水凝胶的生成能力比典型的等渗盐水溶液大几倍。部分RONS迅速释放到受体介质中，因此必须特别注意具有原位交联的水凝胶的设计。值得注意的是，水凝胶显示出持续释放ron的能力。等离子体处理的水凝胶保持完全的生物相容性（由于等离子体产生的物质先前被冲走了），这表明聚合物上没有发生细胞毒性修饰。此外，藻酸盐溶液中产生的ron对骨癌细胞具有细胞毒性。这些结果为在cap相关治疗中使用基于水凝胶的生物材料打开了大门。
In the last years, great advances have been made in therapies based in cold atmospheric plasmas (CAP). CAP generate reactive oxygen and nitrogen species (RONS) which can be transferred to liquids. These CAP activated liquids display the same biological efficacy (i.e. on killing cancer cells) as CAP themselves, opening the door for minimally invasive therapies. However, injection of a liquid in the body results in fast diffusion due to extracellular fluids and blood flow. Therefore, the development of efficient vehicles which allow local confinement and delivery of RONS to the diseased site is a fundamental requirement. In this work, we investigate the generation of RONS (H2O2, NO2-, short-lived RONS) in alginate hydrogels by comparing two atmospheric pressure plasma jets: kINPen and a helium needle, at a range of plasma treatment conditions (time, gas flow, distance to the sample). The physic-chemical properties of the hydrogels remain unchanged by the plasma treatment, while the hydrogel shows several-fold larger capacity for generation of RONS than a typical isotonic saline solution. Part of the RONS are quickly released to a receptor media, so special attention has to be put on the design of hydrogels with in-situ crosslinking. Remarkably, the hydrogels show capacity for sustained release of the RONS. The plasma-treated hydrogels remain fully biocompatible (due the fact that the species generated by plasma are previously washed away), indicating that no cytotoxic modifications have occurred on the polymer. Moreover, the RONS generated in alginate solutions showed cytotoxic potential towards bone cancer cells. These results open the door for the use of hydrogel-based biomaterials in CAP-associated therapies.