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, ¹H 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.

中文翻译：

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酸活化的蜂毒肽用于靶向和安全的抗肿瘤治疗

蜂毒素（MLT）作为一种天然的活性生物分子，可以穿透肿瘤细胞膜在癌症治疗中发挥作用，并且在抗肿瘤药物的未来开发中将引起更多关注。通过在MLT（MLT-DMMA）的2,3-二甲基马来酰亚胺（DMMA）和赖氨酸（Lys）之间引入pH敏感的酰胺键，可以修饰天然蜂毒MLT的主要成分。MLT及其相应的修饰肽MLT-DMMA用于抗肿瘤和生物相容性验证。生物材料特性通过MALDI-TOF MS测试，¹1 H NMR，IUPAC和HPLC，细胞活力，溶血性和动物实验安全性评估。与初级蜂毒肽相比，修饰的肽在生理条件下显示出降低的表面电荷和低的细胞毒性。此外，细胞分析证实了酰胺键的酸活化转化导致了分娩过程中足够的安全性和及时的抗肿瘤活性。因此，MLT-DMMA提供了一个可行的平台，以改善针对性和安全性的抗肿瘤应用。