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随着纳米银敷料的广泛研究，其毒性是一个无法忽视的问题。以前认为纳米银的毒性是银离子和银纳米粒子的联合作用[45]，但最近的一项研究证明纳米银的毒性完全是由银离子的释放引起的[46]。银纳米粒子与水分或伤口渗出液接触后在伤口表面被氧化，并释放银离子。这些离子附着在细菌细胞膜上，通过与细菌膜中的硫蛋白相互作用引起膜的损伤，并进入细菌内，破坏DNA[47-48]。它攻击细菌的呼吸链，抑制细胞分裂，并最终导致细胞死亡。银离子可以产生自由基，并诱导氧化应激进一步促进杀菌活动。图2显示以纳米银为代表的金属敷料的抗菌机制。但纳米银可能对人类真核细胞有相同的效果，研究表明纳米银水凝胶敷料对人皮肤成纤维细胞的细胞毒作用呈浓度依赖性[49]。因此，建立一个治疗窗，银被控制在一个范围内，既可以抑制细菌，又不会对人体细胞产生毒性，这对于壳聚糖基纳米银水凝胶的应用是一个极为关键的问题。
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