Despite exhibiting potent anticancer activity, the strong hemolytic properties of melittin (MEL) significantly restrict its delivery efficiency and clinical applications. To address this issue, we have devised a strategy wherein homologous dopamine (DA), an essential component of bee venom, is harnessed as a vehicle for the synthesis of MEL–polydopamine (PDA) nanoparticles (MP NPs). The ingenious approach lies in the fact that MEL is a basic polypeptide, and the polymerization of DA is also conducted under alkaline conditions, indicating the distinctive advantages of PDA in MEL encapsulation. Furthermore, MP NPs are modified with folic acid to fabricate tumor-targeted nanomedicine (MPF NPs). MPF NPs can ameliorate the hemolysis of MEL in drug delivery and undergo degradation triggered by high levels of reactive oxygen species (ROS) within solid tumors, thereby facilitating MEL release and subsequent restoration of anticancer activity. After cellular uptake, MPF NPs induce cell apoptosis through the PI3K/Akt-mediated p53 signaling pathway. The tumor growth inhibitory rate of MPF NPs in FA receptor-positive 4T1 and CT26 xenograft mice reached 78.04% and 81.66%, which was significantly higher compared to that in FA receptor-negative HepG2 xenograft mice (45.79%). Homologous vehicles provide a new perspective for nanomedicine design.

中文翻译：

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同源聚多巴胺改善蜂毒肽溶血，增强其抗癌功效

尽管蜂毒肽（MEL）表现出有效的抗癌活性，但其强溶血特性严重限制了其递送效率和临床应用。为了解决这个问题，我们设计了一种策略，其中利用蜂毒的重要成分同源多巴胺 (DA) 作为合成 MEL-聚多巴胺 (PDA) 纳米颗粒 (MP NP) 的载体。巧妙之处在于MEL是碱性多肽，而DA的聚合也是在碱性条件下进行的，这表明PDA在MEL封装方面具有独特的优势。此外，MP NPs 用叶酸修饰来制造肿瘤靶向纳米药物（MPF NPs）。 MPF NPs可以改善MEL在药物输送过程中的溶血，并经历实体瘤内高水平活性氧（ROS）引发的降解，从而促进MEL释放并随后恢复抗癌活性。细胞摄取后，MPF NP 通过 PI3K/Akt 介导的 p53 信号通路诱导细胞凋亡。 MPF NPs对FA受体阳性4T1和CT26移植瘤小鼠的肿瘤生长抑制率分别达到78.04%和81.66%，明显高于FA受体阴性HepG2移植瘤小鼠的肿瘤生长抑制率（45.79%）。同源载体为纳米医学设计提供了新的视角。