Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

中文翻译：

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递送装载蜂毒肽的 niosomes 用于治疗乳腺癌：抗癌效果的体外和体内评价

蜂毒肽是蜜蜂毒液的一种肽成分，是一种有吸引力的癌症治疗候选药物。在目前的研究中，蜂毒肽、装载蜂毒肽的 niosome 和空 niosome 已被优化，并在体外对 4T1 和 SKBR3 乳腺细胞系和体内对 BALB/C 近交小鼠的抗癌作用进行了评估。niosomes的制备采用“薄层水化法”；制备了蜂毒肽的不同 niosomal 制剂，并在形态、大小、多分散指数、包封效率、释放动力学和稳定性方面进行了表征。一种 niosome 被配制并装载有蜂毒肽，作为一种用于乳腺癌细胞化疗的有前途的药物载体系统。溶血、细胞凋亡、细胞毒性、选定浓度的蜂毒肽的侵袭和迁移，使用溶血活性测定、流式细胞术、MTT 测定、软琼脂集落测定和伤口愈合测定在 4T1 和 SKBR3 细胞上评估了蜂毒肽和负载蜂毒肽的 niosome。实时PCR用于确定基因表达。使用了 40 只 BALB/c 近交系小鼠；然后，对所有组进行了组织病理学、P53 免疫组织化学测定和肾和肝酶活性的估计。该研究表明，由于靶向性、包封率​​、PDI 和释放率的提高，装载蜂毒肽的 niosome 是乳腺癌治疗的绝佳替代品，并且对细胞系具有很高的抗癌作用。加载蜂毒肽的niosome对研究细胞基因表达的影响高于其他样品；下调 Bcl2、MMP2 和 MMP9 基因的表达，同时上调 Bax、Caspase3 和 Caspase9 基因的表达。与蜂毒肽样品相比，它们还提高了细胞凋亡率并抑制了两种细胞系中的细胞迁移和侵袭。组织病理学结果显示负载蜂毒肽的 niosome 有丝分裂指数、侵袭和多形性降低。与健康对照相比，装载蜂毒肽的 niosome 和蜂毒肽的肾脏和肝脏生物标志物活性没有显着差异。在免疫组织化学中，P53 表达在所有组中均未显示出显着变化。我们的研究成功地表明，加载蜂毒肽的 niosome 比游离蜂毒肽具有更多的抗癌作用。该项目已经证明，与游离形式相比，niosomes 是蜂毒肽的合适囊泡载体。组织病理学结果显示负载蜂毒肽的 niosome 有丝分裂指数、侵袭和多形性降低。与健康对照相比，装载蜂毒肽的 niosome 和蜂毒肽的肾脏和肝脏生物标志物活性没有显着差异。在免疫组织化学中，P53 表达在所有组中均未显示出显着变化。我们的研究成功地表明，加载蜂毒肽的 niosome 比游离蜂毒肽具有更多的抗癌作用。该项目已经证明，与游离形式相比，niosomes 是蜂毒肽的合适囊泡载体。组织病理学结果显示负载蜂毒肽的 niosome 有丝分裂指数、侵袭和多形性降低。与健康对照相比，装载蜂毒肽的 niosome 和蜂毒肽的肾脏和肝脏生物标志物活性没有显着差异。在免疫组织化学中，P53 表达在所有组中均未显示出显着变化。我们的研究成功地表明，加载蜂毒肽的 niosome 比游离蜂毒肽具有更多的抗癌作用。该项目已经证明，与游离形式相比，niosomes 是蜂毒肽的合适囊泡载体。我们的研究成功地表明，加载蜂毒肽的 niosome 比游离蜂毒肽具有更多的抗癌作用。该项目已经证明，与游离形式相比，niosomes 是蜂毒肽的合适囊泡载体。我们的研究成功地表明，加载蜂毒肽的 niosome 比游离蜂毒肽具有更多的抗癌作用。该项目已经证明，与游离形式相比，niosomes 是蜂毒肽的合适囊泡载体。