Protein-based nanoparticles (NPs), especially albumin NPs, are effective and safe drug carriers. Non-covalently assembled albumin NPs prepared by the nanoparticle albumin-bound (nab) technology possess higher tumor targeting efficiency compared to crosslinked albumin NPs. However, the production process of protein NPs by the nab technology is rather complicated and involves toxic chemicals. Moreover, the mechanisms behind the assembly of albumin induced by the nab technology are far from elucidated. We hypothesized that hydroxyl radical may facilitate the formation of protein NPs prepared by the nab technology. Based on that, a novel and green method was developed to produce protein NPs by controlled hydroxyl radical oxidation via Fenton reaction through one-step mixing. The resulted bovine serum albumin (BSA) NPs were revealed as a non-covalent assembly of BSA molecules with hydrophobic interaction as the driven force for the NPs formation. The Fenton method of BSA NPs production was facile to produce the lipophilic drug paclitaxel (PTX) loaded BSA NPs (PTX@BSA NPs), which exhibited promising antitumor efficacy, pharmacokinetic and safety profiles. Besides BSA, the Fenton method was applicable to other proteins including casein, beta-lactoglobulin and keratin. Thus, the one-step Fenton methodology offers a unique green solution to produce non-crosslinking protein NPs as effective drug carriers for biomedical applications.

基于蛋白质的纳米颗粒（NP），尤其是白蛋白NP，是有效且安全的药物载体。与交联的白蛋白NP相比，通过纳米颗粒白蛋白结合（nab）技术制备的非共价组装的白蛋白NP具有更高的肿瘤靶向效率。然而，通过nab技术生产蛋白质NP的过程相当复杂，并且涉及有毒化学物质。而且，由nab技术诱导的白蛋白组装背后的机制还远未阐明。我们假设羟基自由基可以促进通过nab技术制备的蛋白质NP的形成。在此基础上，开发了一种新颖的绿色方法，通过一步混合通过Fenton反应，通过受控的羟基自由基氧化来生产蛋白质NP。所得的牛血清白蛋白（BSA）NPs被​​揭示为BSA分子的非共价组装体，其疏水相互作用是NPs形成的驱动力。用Fenton法生产BSA NP的方法很容易生产载有亲脂性药物紫杉醇（PTX）的BSA NP（PTX @ BSA NP），该药物显示出有希望的抗肿瘤功效，药代动力学和安全性。除BSA外，Fenton方法还适用于酪蛋白，β-乳球蛋白和角蛋白等其他蛋白质。因此，一步式Fenton方法论提供了一种独特的绿色解决方案，可生产非交联蛋白NP作为生物医学应用的有效药物载体。用Fenton法生产BSA NP的方法很容易生产载有亲脂性药物紫杉醇（PTX）的BSA NP（PTX @ BSA NP），该药物显示出有希望的抗肿瘤功效，药代动力学和安全性。除BSA外，Fenton方法还适用于酪蛋白，β-乳球蛋白和角蛋白等其他蛋白质。因此，一步式Fenton方法论提供了一种独特的绿色解决方案，可生产非交联蛋白NP作为生物医学应用的有效药物载体。用Fenton法生产BSA NP的方法很容易生产载有亲脂性药物紫杉醇（PTX）的BSA NP（PTX @ BSA NP），该药物显示出有希望的抗肿瘤功效，药代动力学和安全性。除BSA外，Fenton方法还适用于酪蛋白，β-乳球蛋白和角蛋白等其他蛋白质。因此，一步式Fenton方法论提供了一种独特的绿色解决方案，可生产非交联蛋白NP作为生物医学应用的有效药物载体。