Self-Templated, Green-Synthetic, Size-Controlled Protein Nanoassembly as a Robust Nanoplatform for Biomedical Application
Self-Templated, Green-Synthetic, Size-Controlled Protein Nanoassembly as a Robust Nanoplatform for Biomedical Application
复制标题
自模板化、绿色合成、尺寸控制的蛋白质纳米组装作为生物医学应用的稳健纳米平台
DOI：
10.1021/acsami.7b19201
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发表时间：
2018
影响因子：
9.5
通讯作者：
Li Yongyong
中科院分区：
文献类型：
--
作者：
Wen Ya;Dong Haiqing;Wang Kun;Li Yan;Li Yongyong
尽管蛋白质纳米粒子与合成聚合物相比具有固有的优势，但由于其尺寸控制较低、使用有毒交联剂或有机溶剂等原因，在制造过程中仍不能令人满意。这在一定程度上导致了亚伯拉沙星在临床上的边际效益。在这里，开发了一种绿色合成、尺寸可控的方法来制备稳定的白蛋白纳米颗粒。物理堆积的卵清蛋白纳米簇在加热过程中暂时形成，然后以此为模板形成分子间二硫键网络化学稳定的蛋白质纳米颗粒。将游离硫醇嵌入到疏水白蛋白结构中，并将其氧化成二硫化物(在此过程中，硫醇基团减少了2-3倍)是这一过程中的关键因素。在十二烷基硫酸钠(疏水破坏剂)处理下结构稳定，而在还原条件下(裂解二硫化物)快速解离，验证了二硫键交联机理。所开发的方法简单、重复性好，具有精确的尺寸控制(从几十纳米到数百纳米)。该方法可以扩展到其他蛋白质，如牛血清白蛋白，强调了潜在的普遍适用性。进一步的研究表明，合成的蛋白质纳米颗粒可以作为一个强大的纳米平台，用于广泛的生物医学应用，包括药物输送(阿霉素包封率为5.7%)、靶向生物偶联或强大的免疫佐剂效应。
Despite inherent advantages over their synthetic polymer-based counterparts, protein nanoparticles remain unsatisfactory in fabrication owing to their low size control, usage of toxic cross-linkers, or organic solvents. This partially contributes to the marginal benefits of Abraxane in clinics. Herein, a green-synthetic, size-controlled approach was developed to generate stable albumin nanoparticles. Physically packed ovalbumin nanoclusters were temporally formed in heat, which was then used as the template to form protein nanoparticles chemically stabilized by the intermolecular disulfide network. Exposure of embedded free thiols within a hydrophobic albumin structure and oxidation of them into disulfides (2–3 fold reduction of thiols groups in this process) were identified as key factors during the process. The fact that the structure was stable in sodium dodecyl sulfate treatment (hydrophobic destroyer) while disassembling fast in reduction condition (to cleave disulfide) validated the disulfide cross-linked mechanism. The developed approach is facile and reproducible with precision size control (from tens to hundreds of nanometers). The approach can be extended to other proteins such as bovine serum albumin, underscoring the potential universal applicability. Further study demonstrated that the resultant protein nanoparticles can be a robust nanoplatform for extensive biomedical applications including drug delivery (doxorubicin encapsulation of 5.7%), target bioconjugation, or robust immune adjuvant effect.