Lee Fan, Chung Joo Eun, Xu Keming, Kurisawa Motoichi
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.
ACS Macro Lett. 2015 Sep 15;4(9):957-960. doi: 10.1021/acsmacrolett.5b00544. Epub 2015 Aug 21.
The oxidative coupling of phenols by horseradish peroxidase (HRP) is widely utilized to cross-link polymer-phenol conjugates for hydrogel formation. Phenols containing one aromatic ring are most commonly used, and the addition of hydrogen peroxide (HO) is an indispensable step in catalyzing the enzymatic reaction. We describe here a hydrogel composed of polyphenol as the cross-linking moiety. (-)-Epigallocatechin-3-gallate (EGCG), a green tea catechin, was conjugated to hyaluronic acid (HA) to form HA-EGCG conjugates. Addition of HRP to a solution of HA-EGCG conjugates at pH 7.4 induced gelation in 7 min. Notably, the addition of exogenous HO was not required, as HO was generated via EGCG autoxidation. Moreover, cross-linking between HA-EGCG conjugates occurred in situ through EGCG quinone formation, even when no HRP was added. This approach of forming hydrogels circumvented the safety concern associated with HRP due to its plant origin. Furthermore, the EGCG moieties endowed the hydrogels with resistance toward hyaluronidase-mediated degradation in vivo.
辣根过氧化物酶（HRP）催化的酚类氧化偶联反应被广泛用于交联聚合物-酚类共轭物以形成水凝胶。最常用的是含有一个芳环的酚类，而过氧化氢（HO）的添加是催化酶促反应必不可少的一步。我们在此描述一种以多酚为交联部分的水凝胶。（-）-表没食子儿茶素-3-没食子酸酯（EGCG），一种绿茶儿茶素，与透明质酸（HA）共轭形成HA-EGCG共轭物。在pH 7.4的HA-EGCG共轭物溶液中加入HRP，7分钟内即可诱导凝胶化。值得注意的是，不需要添加外源HO，因为HO是通过EGCG自氧化产生的。此外，即使不添加HRP，HA-EGCG共轭物之间也会通过EGCG醌的形成原位发生交联。这种形成水凝胶的方法避免了由于HRP来源于植物而产生的安全问题。此外，EGCG部分赋予水凝胶在体内抵抗透明质酸酶介导的降解的能力。
