Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, 6th October City, 12578, Giza, Egypt.
Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
Life Sci. 2023 Mar 1;316:121379. doi: 10.1016/j.lfs.2023.121379. Epub 2023 Jan 7.
Breast cancer represents one of the top lethal cancer types among the females worldwide. Several factors manipulate the clinical outcome of the treatment as the stage of the cancer upon detection, genetic and hormonal factors, drug resistance and metastasis. Accordingly, drug's repositioning, enhancing the bioavailability and encapsulation into nanoparticles (NPs) are among the predilected pathways for enhanced therapeutic outcome. Niclosamide (NIC) is an anthelmintic drug and has been repositioned as anticancer agent after revealing its anti-neoplastic activity. Piperine (PIP) was used as food spice until its anticancer activity was discovered. However, their hydrophobicity constrains their therapeutic efficiency. The cytotoxicity of both drugs in the free form was tested on MCF-7 cells, and the results indicated a NIC cytotoxicity enhancement by PIP. Then, NIC and PIP were encapsulated successfully into F127-NPs with entrapment efficiency of 97 % and 82 %, respectively. Particle size, zeta potential, TEM and FTIR confirmed the micellization process and drug encapsulation. The developed NIC-NPs and PIP-NPs exerted potent anticancer effect as compared to the free forms. Accordingly, the mixture; NIC-NPs/PIP-NPs was tested and its cytotoxicity exceeded the individually encapsulated drugs. Flowcytometry assessment was performed and demonstrated an induced cell death through the apoptotic stage. Additionally, in-vivo therapeutic efficiency of NIC-NPs/PIP-NPs was assessed through Ehrlich ascites tumor and the nanocombination therapy exerted superior additive anticancer effect when compared to NIC-NPs which is attributed to the PIP-NPs induced bioavailability. The study can be considered the first one investigating the PIP role in bioenhancing the anti-proliferative activity of NIC to combat breast cancer.
乳腺癌是全球女性中致死率最高的癌症之一。有几个因素会影响治疗的临床效果，如癌症发现时的阶段、遗传和激素因素、耐药性和转移。因此，药物再定位、提高生物利用度和包封成纳米颗粒 (NPs) 是增强治疗效果的首选途径之一。氯硝柳胺 (NIC) 是一种驱虫药，在发现其抗肿瘤活性后被重新定位为抗癌药物。胡椒碱 (PIP) 曾被用作食品香料，直到其抗癌活性被发现。然而，它们的疏水性限制了它们的治疗效果。在 MCF-7 细胞中测试了这两种药物在游离形式下的细胞毒性，结果表明 PIP 增强了 NIC 的细胞毒性。然后，成功地将 NIC 和 PIP 分别封装到 F127-NPs 中，包封效率分别为 97%和 82%。粒径、zeta 电位、TEM 和 FTIR 证实了胶束化过程和药物包封。与游离形式相比，所开发的 NIC-NPs 和 PIP-NPs 发挥了更强的抗癌作用。因此，测试了 NIC-NPs/PIP-NPs 的混合物，其细胞毒性超过了单独封装的药物。流式细胞术评估表明，通过凋亡阶段诱导细胞死亡。此外，通过艾氏腹水瘤评估了 NIC-NPs/PIP-NPs 的体内治疗效果，纳米组合疗法的抗癌效果优于 NIC-NPs，这归因于 PIP-NPs 诱导的生物利用度。这项研究可以被认为是第一个研究 PIP 在增强 NIC 的抗增殖活性以对抗乳腺癌方面的作用的研究。
