Liu Kegang, Wang Xueya, Li-Blatter Xiaochun, Wolf Marc, Hunziker Patrick
Nanomedicine Research Lab CLINAM, University of Basel, University Hospital Basel, Bernoullistrasse 20, CH-4056 Basel, Switzerland.
Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
ACS Appl Bio Mater. 2020 Oct 19;3(10):6919-6931. doi: 10.1021/acsabm.0c00808. Epub 2020 Oct 5.
Nanomaterials allow designing targeted therapies, facilitate molecular diagnostics, and are therefore enabling platforms for personalized medicine. A systematic science and a predictive understanding of molecular/supramolecular structure relationships and nanoparticle structure/biological property relationships are needed for rational design and clinical progress but are hampered by the anecdotal nature, nonsystematic and nonrepresentative nanomaterial assortment, and oligo-disciplinary approach of many publications. Here, we find that a systematic and comprehensive multidisciplinary approach to production and exploration of molecular-structure/nanostructure relationship and nano-bio structure/function relationship of medical nanomaterials can be achieved by combining systematic chemical synthesis, thorough physicochemical analysis, computer modeling, and biological experiments, as shown in a nanomaterial family of amphiphilic, micelle-forming oxazoline/siloxane block copolymers suited for the clinical application. This comprehensive interdisciplinary approach leads to improved understanding of nanomaterial structures, allows good insights into binding modes for the nanomaterial protein corona, induces the design of minimal cell-binding materials, and yields rational strategies to avoid toxicity. Thus, this work contributes to a systematic and scientific basis for rational design of medical nanomaterials.
纳米材料有助于设计靶向疗法，促进分子诊断，因此是个性化医疗的支撑平台。要进行合理设计并取得临床进展，需要对分子/超分子结构关系以及纳米颗粒结构/生物学特性关系有系统的科学认识和预测性理解，但许多出版物的轶事性质、非系统性和非代表性的纳米材料分类以及多学科方法的局限性阻碍了这一进程。在这里，我们发现，通过结合系统化学合成、全面的物理化学分析、计算机建模和生物学实验，可以实现对医用纳米材料的分子结构/纳米结构关系以及纳米生物结构/功能关系进行系统而全面的多学科生产和探索，如在适用于临床应用的两亲性、形成胶束的恶唑啉/硅氧烷嵌段共聚物纳米材料家族中所示。这种全面的跨学科方法有助于更好地理解纳米材料结构，深入了解纳米材料蛋白质冠的结合模式，诱导设计最小细胞结合材料，并产生避免毒性的合理策略。因此，这项工作为医用纳米材料的合理设计提供了系统的科学依据。
