OBJECTIVE Dermaseptin-PP is a newly discovered anticancer peptide with a unique antitumour mechanism and remarkable effect. However, this α-helix anticancer peptide risks haemolysis when used at high doses, which limits its further application. This study aims to prepare a pH-responsive liposome, Der-loaded-pHSL, using nanotechnology to avoid the haemolysis risk of Dermaseptin-PP and increase its accumulation in tumour sites to enhance efficacy and reduce toxicity. METHODS The characterisation of Der-loaded-pHSL was carried out employing preparation. The effect of haemolysis and tumour inhibition were investigated by in vitro haemolysis assay and cytotoxicity assay. The cell uptake under different pH conditions was investigated by flow cytometry, and the effect of pH on tumour cell selectivity was evaluated. In order to evaluate the in vivo targeting and antitumour effect of Der-loaded-pHSL, the in vivo distribution experiment and the pharmacodynamic experiment were performed using the nude mouse tumour model. RESULTS The preparation method of the Der-loaded-pHSL is simple, and the liposome has good nanoparticle characteristics. When Dermaseptin-PP was prepared as liposome, haemolysis was significantly decreased, and tumour cell inhibition was significantly enhanced. Compared with ordinary liposomes, this change was more significant in Der-loaded-pHSL. The uptake of pH-sensitive liposomes was higher in the simulated acidic tumour microenvironment, and the uptake showed a specific acid dependence. In vivo experiments showed that Der-loaded-pHSL had a significant tumour-targeting effect and could significantly enhance the antitumour effect of Dermaseptin-PP. CONCLUSION Der-loaded-pHSL designed in this study is a liposome with a quick, simple, effective preparation method, which can significantly reduce the haemolytic toxicity of Dermaseptin-PP and enhance its antitumour effect by increasing the tumour accumulation and cell intake. It provides a new idea for applying Dermaseptin-PP and other anticancer peptides with α-helical structure.

中文翻译：

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刺激响应纳米脂质体增强新型肽 Dermaseptin-PP 的抗肿瘤作用。

目的Dermaseptin-PP是一种新发现的抗癌肽，具有独特的抗肿瘤机制和显着的效果。然而，这种α-螺旋抗癌肽在高剂量使用时存在溶血风险，限制了其进一步应用。本研究旨在利用纳米技术制备pH响应性脂质体Der-loaded-pHSL，避免Dermaseptin-PP的溶血风险，并增加其在肿瘤部位的积累，以增强疗效并降低毒性。方法采用制备方法对Der-loaded-pHSL进行表征。通过体外溶血试验和细胞毒性试验考察其溶血和抑瘤作用。采用流式细胞术研究不同pH条件下的细胞摄取情况，评价pH对肿瘤细胞选择性的影响。为了评价Der-loaded-pHSL的体内靶向和抗肿瘤作用，利用裸鼠肿瘤模型进行了体内分布实验和药效实验。结果Der-loaded-pHSL的制备方法简单，脂质体具有良好的纳米颗粒特性。当Dermaseptin-PP制备成脂质体时，溶血作用显着减少，肿瘤细胞抑制作用显着增强。与普通脂质体相比，Der-loaded-pHSL 中这种变化更为显着。pH敏感脂质体在模拟酸性肿瘤微环境中的摄取较高，且摄取表现出特定的酸依赖性。体内实验表明，Der-loaded-pHSL具有显着的肿瘤靶向作用，并能显着增强Dermaseptin-PP的抗肿瘤作用。结论本研究设计的Der-loaded-pHSL是一种快速、简单、有效的制备方法的脂质体，可显着降低Dermaseptin-PP的溶血毒性，通过增加肿瘤蓄积和细胞摄取来增强其抗肿瘤作用。为Dermaseptin-PP等α螺旋结构抗癌肽的应用提供了新思路。