Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Acta Biomater. 2012 Sep;8(9):3241-50. doi: 10.1016/j.actbio.2012.05.021. Epub 2012 May 27.
Self-assembling peptide nanofibers have emerged as important nanobiomaterials, with such applications as delivery of therapeutic agents and vaccines, nanofabrication and biomineralization, tissue engineering and regenerative medicine. Recently a new class of self-assembling peptides has been introduced, which takes into consideration amino acid pairing (AAP) strategies in the peptide sequence design. Even though these peptides have shown promising potential in the design of novel functional biomaterials, they have a propensity to initiate uncontrollable aggregation and be degraded by proteolytic enzymes. These present the most significant challenge in advancing self-assembling peptides for in vitro and in vivo applications. Functionalizing biomaterials with polyethylene glycol (PEG) has been shown to surmount such problems. Here the results of conjugating diethylene glycol (DEG), a short segment of PEG, to one of the AAP peptides, AAP8, with eight amino acids in sequence, are reported. The results indicate that incorporation of DEG into the peptide sequence modulates fiber self-assembly through creating more aligned and uniform nanostructures. This is associated with increasing solubility, stability, and secondary structure β-sheet content of the peptide. The DEG conjugate of AAP8 also shows reduced cellular cytotoxicity. Functionalization of AAP8 improves the capability of the peptide to stabilize and deliver a hydrophobic anticancer compound, ellipticine, in aqueous solution, consequently inducing greater cytotoxicity to lung carcinoma cells over a relatively long time, compared with non-functionalized AAP8. The presented functionalized peptide and its drug delivery application indicate a potentially useful design strategy for novel self-assembling peptide biomaterials for biotechnology and nanomedicine.
自组装肽纳米纤维已成为重要的纳米生物材料，具有递送治疗剂和疫苗、纳米制造和生物矿化、组织工程和再生医学等应用。最近，引入了一类新的自组装肽，该肽在肽序列设计中考虑了氨基酸配对 (AAP) 策略。尽管这些肽在设计新型功能性生物材料方面显示出了有前景的潜力，但它们有引发不可控聚集和被蛋白水解酶降解的倾向。这是将自组装肽推进用于体外和体内应用的最重大挑战。用聚乙二醇 (PEG) 对生物材料进行功能化已被证明可以克服这些问题。这里报道了将二甘醇 (DEG)，即 PEG 的一个短片段，连接到具有 8 个氨基酸序列的 AAP 肽之一 AAP8 的结果。结果表明，通过创建更对齐和均匀的纳米结构，将 DEG 掺入肽序列中会调节纤维自组装。这与肽的溶解性、稳定性和二级结构β-折叠含量的增加有关。AAP8 的 DEG 缀合物还显示出降低的细胞毒性。AAP8 的功能化提高了肽稳定和递送疏水性抗癌化合物椭圆素的能力，与非功能化的 AAP8 相比，在相对较长的时间内，能够诱导肺癌细胞产生更大的细胞毒性。所提出的功能化肽及其药物递送应用为生物技术和纳米医学中的新型自组装肽生物材料提供了一种潜在有用的设计策略。
