Mansour Amira, Mahmoud Mohamed Y, Bakr Alaa F, Ghoniem Monira G, Adam Fatima A, El-Sherbiny Ibrahim M
Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science & Technology, Giza 12578, Egypt.
Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
Pharmaceutics. 2022 Nov 30;14(12):2668. doi: 10.3390/pharmaceutics14122668.
Breast cancer is a prevalent tumor and causes deadly metastatic complications. Myriad cancer types, including breast cancer, are effectively treated by methotrexate (MTX). However, MTX hydrophobicity, adverse effects and the development of resistance have inspired a search for new effective strategies to overcome these challenges. These may include the addition of a bioenhancer and/or encapsulation into appropriate nano-based carriers. In the present study, the anticancer effect of MTX was fortified through dual approaches. First, the concomitant use of piperine (PIP) as a bioenhancer with MTX, which was investigated in the MCF-7 cell line. The results depicted significantly lower IC values for the combination (PIP/MTX) than for MTX. Second, PIP and MTX were individually nanoformulated into F-127 pluronic nanomicelles (PIP-NMs) and F-127/P-105 mixed pluronic nanomicelles (MTX-MNMs), respectively, validated by several characterization techniques, and the re-investigated cytotoxicity of PIP-NMs and MTX-MNMs was fortified. Besides, the PIP-NMs/MTX-MNMs demonstrated further cytotoxicity enhancement. The PIP-NMs/MTX-MNMs combination was analyzed by flow cytometry to understand the cell death mechanism. Moreover, the in vivo assessment of PIP-NMs/MTX-MNMs was adopted through the Ehrlich ascites model, which revealed a significant reduction of the tumor weight. However, some results of the tumor markers showed that the addition of PIP-NMs to MTX-MNMs did not significantly enhance the antitumor effect.
乳腺癌是一种常见肿瘤，会引发致命的转移并发症。包括乳腺癌在内的多种癌症类型都可以通过甲氨蝶呤（MTX）得到有效治疗。然而，MTX的疏水性、副作用以及耐药性的产生促使人们寻找新的有效策略来克服这些挑战。这些策略可能包括添加生物增强剂和/或将其封装到合适的纳米载体中。在本研究中，通过两种方法增强了MTX的抗癌效果。首先，在MCF-7细胞系中研究了将胡椒碱（PIP）作为生物增强剂与MTX联合使用。结果表明，联合用药（PIP/MTX）的IC值显著低于MTX。其次，分别将PIP和MTX纳米制备成F-127普朗尼克纳米胶束（PIP-NMs）和F-127/P-105混合普朗尼克纳米胶束（MTX-MNMs），并通过多种表征技术进行了验证，再次研究发现PIP-NMs和MTX-MNMs的细胞毒性增强。此外，PIP-NMs/MTX-MNMs表现出进一步的细胞毒性增强。通过流式细胞术分析PIP-NMs/MTX-MNMs组合以了解细胞死亡机制。此外，通过艾氏腹水模型对PIP-NMs/MTX-MNMs进行体内评估，结果显示肿瘤重量显著减轻。然而，一些肿瘤标志物的结果表明，在MTX-MNMs中添加PIP-NMs并没有显著增强抗肿瘤效果。
