Site-Specific Biomimicry of Antioxidative Melanin Formation and Its Application for Acute Liver Injury Therapy and Imaging
Site-Specific Biomimicry of Antioxidative Melanin Formation and Its Application for Acute Liver Injury Therapy and Imaging
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抗氧化黑色素形成的位点特异性仿生及其在急性肝损伤治疗和成像中的应用
DOI：
10.1002/adma.202102391
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Shi Jinjun
中科院分区：
文献类型：
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作者：
Zhao Caiyan;Li Zhi;Chen Jingxiao;Su Lichao;Wang Junqing;Chen Dean Shuailin;Ye Jiamin;Liao Naishun;Yang Huanghao;Song Jibin;Shi Jinjun
由天然分子/材料（例如多巴胺和黑色素）组成的生物相容性纳米抗氧化剂在多种生物医学应用中引起了极大的兴趣。然而，缺乏对这些生物材料的精确结构以及有效成分的实际剂量的了解阻碍了它们的转化。本文报道了一种模拟原位黑色素形成并探索其抗氧化应用的策略，通过开发聚乙二醇化、苯基硼酸保护的 L-DOPA 前体 (PAD)，该前体可以自组装成明确的纳米颗粒 (PADN)。暴露于氧化物质会导致苯基硼酸脱保护，将 PADN 转化为 PEG-L-DOPA，其与黑色素的生物合成途径类似，可以被氧化并聚合成抗氧化黑色素样结构。 PADN具有超高的稳定性和优异的抗氧化活性，在预防和治疗急性肝损伤/衰竭方面显示出显着的功效。此外，原位结构转变使 PADN 能够通过光声成像无创地可视化受损组织。总体而言，描述了一种具有精确结构和位点特异性生物活性的生物启发抗氧化剂，用于氧化应激相关疾病的治疗诊断。
Biocompatible nano‐antioxidants composed of natural molecules/materials, such as dopamine and melanin, are of great interest for diverse biomedical applications. However, the lack of understanding of the precise structure of these biomaterials and thus the actual dose of effective components impedes their advancement to translation. Herein, a strategy to mimic in situ melanin formation and explore its antioxidative applications is reported, by developing a PEGylated, phenylboronic‐acid‐protected L‐DOPA precursor (PAD) that can self‐assemble into well‐defined nanoparticles (PADN). Exposure to oxidative species leads to deprotection of phenylboronic acids, transforming PADN to PEG‐L‐DOPA, which, similar to the biosynthetic pathway of melanin, can be oxidized and polymerized into an antioxidative melanin‐like structure. With ultrahigh stability and superior antioxidative activity, the PADN shows remarkable efficacy in prevention and treatment of acute liver injury/failure. Moreover, the in situ structure transformation enables PADN to visualize damaged tissue noninvasively by photoacoustic imaging. Overall, a bioinspired antioxidant with precise structure and site‐specific biological activity for theranostics of oxidative stress‐related diseases is described.