Ju Yi, Cui Jiwei, Sun Huanli, Müllner Markus, Dai Yunlu, Guo Junling, Bertleff-Zieschang Nadja, Suma Tomoya, Richardson Joseph J, Caruso Frank
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
Key Centre for Polymers and Colloids, School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Biomacromolecules. 2016 Jun 13;17(6):2268-76. doi: 10.1021/acs.biomac.6b00537. Epub 2016 Jun 1.
We engineered metal-phenolic capsules with both high targeting and low nonspecific cell binding properties. The capsules were prepared by coating phenolic-functionalized hyaluronic acid (HA) and poly(ethylene glycol) (PEG) on calcium carbonate templates, followed by cross-linking the phenolic groups with metal ions and removing the templates. The incorporation of HA significantly enhanced binding and association with a CD44 overexpressing (CD44+) cancer cell line, while the incorporation of PEG reduced nonspecific interactions with a CD44 minimal-expressing (CD44-) cell line. Moreover, high specific targeting to CD44+ cells can be balanced with low nonspecific binding to CD44- cells simply by using an optimized feed-ratio of HA and PEG to vary the content of HA and PEG incorporated into the capsules. Loading an anticancer drug (i.e., doxorubicin) into the obtained capsules resulted in significantly higher cytotoxicity to CD44+ cells but lower cytotoxicity to CD44- cells.
我们设计了具有高靶向性和低非特异性细胞结合特性的金属酚醛胶囊。通过在碳酸钙模板上包覆酚官能化透明质酸（HA）和聚乙二醇（PEG），然后将酚基团与金属离子交联并去除模板来制备胶囊。HA的掺入显著增强了与过表达CD44（CD44 +）癌细胞系的结合和关联，而PEG的掺入减少了与低表达CD44（CD44 -）细胞系的非特异性相互作用。此外，只需使用HA和PEG的优化进料比来改变掺入胶囊中的HA和PEG的含量，就可以在对CD44 +细胞的高特异性靶向与对CD44 -细胞的低非特异性结合之间取得平衡。将抗癌药物（即阿霉素）负载到所得胶囊中，对CD44 +细胞产生了显著更高的细胞毒性，但对CD44 -细胞的细胞毒性较低。
