Protein-based materials are widely used in biomedical applications. Often the proteins need to be crosslinked in order to be stable for application. Here, we explored the use of 5,5′-bisvanillin as a potentially non-toxic crosslinker that can react with lysine residues on proteins. To demonstrate the success of the crosslinking reaction, polymer–protein conjugates based on bovine serum albumin (BSA) and poly(N-isopropyl acrylamide) (PNIPAM) were employed. The BSA-PNIPAM conjugate is water soluble at room temperature, but heated above the cloud point, BSA-PNIPAM forms nanoparticles of around 70 nm that can again disassemble at lower temperatures. Reaction with 5,5′-bisvanillin prevented disassembly resulting in stable BSA nanoparticles of 50 nm in size. The formed nanoparticles were observed to be rather stable and were not easily cleaved in acidic conditions. The crosslinker 5,5′-bisvanillin was measured to have lower toxicity against A2780 lung cancer cell lines compared with the commonly applied crosslinker glutaraldehyde.

蛋白质基材料广泛用于生物医学应用。通常，蛋白质需要交联才能稳定使用。在这里，我们探索了5,5'-双香兰素作为可与蛋白质上的赖氨酸残基反应的潜在无毒交联剂的用途。为了证明交联反应的成功，基于牛血清白蛋白（BSA）和聚（N使用-异丙基丙烯酰胺（PNIPAM）。BSA-PNIPAM共轭物在室温下是水溶性的，但在浊点以上加热，BSA-PNIPAM形成约70 nm的纳米颗粒，可在较低温度下再次分解。与5,5'-双香兰素的反应可防止分解，从而产生尺寸为50 nm的稳定BSA纳米颗粒。观察到形成的纳米颗粒相当稳定，并且在酸性条件下不容易裂解。与常用的交联剂戊二醛相比，测得交联剂5,5'-双香兰素对A2780肺癌细胞系的毒性较低。