Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants , Bioengineering College of Chongqing University , Chongqing 400044 , China.
Institute of Life Sciences , Wenzhou University , Wenzhou 325000 , China.
Bioconjug Chem. 2018 Sep 19;29(9):2936-2944. doi: 10.1021/acs.bioconjchem.8b00352. Epub 2018 Sep 7.
Melittin (MLT), as a natural active biomolecule, can penetrate the tumor cell membrane to play a role in cancer treatment and will attract more attention in future development of antitumor drugs. The main component of natural bee venom MLT was modified by introducing a pH-sensitive amide bond between the 2,3-dimethyl maleimide (DMMA) and the lysine (Lys) of MLT (MLT-DMMA). MLT and its corresponding modified peptide MLT-DMMA were used for antitumor and biocompatibility validation. The biomaterial characteristics were tested by MALDI-TOF MS, H NMR, IUPAC and HPLC, cell viability, hemolytic and animal experiment safety evaluation. Compared with the primary melittin, the modified peptide showed decreased surface charge and low cytotoxicity in physiological conditions. Moreover, cell assays confirmed the acid-activated conversion of amide bond resulting in adequate safety during delivery and timely antitumor activity in tumor lesions. Thus, MLT-DMMA provided a feasible platform to improve the targeted and safe antitumor applications.
蜂毒素（MLT）作为一种天然活性生物分子，能够穿透肿瘤细胞膜，在癌症治疗中发挥作用，在抗肿瘤药物的未来发展中将会受到更多关注。天然蜂毒 MLT 的主要成分通过在 2,3-二甲基马来酰亚胺（DMMA）和 MLT 的赖氨酸（Lys）之间引入 pH 敏感酰胺键进行修饰（MLT-DMMA）。MLT 及其相应的修饰肽 MLT-DMMA 用于抗肿瘤和生物相容性验证。通过 MALDI-TOF MS、H NMR、IUPAC 和 HPLC 测试生物材料特性、细胞活力、溶血和动物实验安全性评估。与原始蜂毒素相比，修饰肽在生理条件下表现出较低的表面电荷和低细胞毒性。此外，细胞实验证实酰胺键的酸激活转化导致在输送过程中有足够的安全性，并在肿瘤病变部位及时发挥抗肿瘤活性。因此，MLT-DMMA 为提高靶向和安全的抗肿瘤应用提供了一个可行的平台。
