Ombredane Alicia Simalie, Martins Natália Ornelas, de Souza Gabriela Mara Vieira, Araujo Victor Hugo Sousa, Szlachetka Ísis O, da Silva Sebastião William, da Rocha Márcia Cristina Oliveira, Oliveira Andressa Souza de, Holanda Cleonice Andrade, Romeiro Luiz Antonio Soares, Damas Elysa Beatriz de Oliveira, Azevedo Ricardo Bentes, Joanitti Graziella Anselmo
Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), University of Brasilia, Campus Universitário-Centro Metropolitano, Ceilandia Sul, Brasilia 72220-275, Brazil.
Post-Graduation Program in Nanoscience and Nanobiotechnology, University of Brasilia, Campus Universitário Darcy Ribeiro, Brasilia 70910-900, Brazil.
Pharmaceutics. 2024 Sep 5;16(9):1170. doi: 10.3390/pharmaceutics16091170.
Combination therapy integrated with nanotechnology offers a promising alternative for breast cancer treatment. The inclusion of pequi oil, anacardic acid (AA), and docetaxel (DTX) in a nanoemulsion can amplify the antitumor effects of each molecule while reducing adverse effects. Therefore, the study aims to develop pequi oil-based nanoemulsions (PeNE) containing DTX (PDTX) or AA (PAA) and to evaluate their cytotoxicity against triple-negative breast cancer cells (4T1) in vitro. The PeNE without and with AA (PAA) and DTX (PDTX) were prepared by sonication and characterized by ZetaSizer and electronic transmission microscopy. Viability testing and combination index (CI) were determined by MTT and Chou-Talalay methods, respectively. Flow cytometry was employed to investigate the effects of the formulations on cell structures. PeNE, PDTX, and PAA showed hydrodynamic diameter < 200 nm and a polydispersity index (PdI) of 0.3. The association PDTX + PAA induced a greater decrease in cell viability (~70%, < 0.0001) and additive effect (CI < 1). In parallel, an association of the DTX + AA molecules led to antagonism (CI > 1). Additionally, PDTX + PAA induced an expressive morphological change, a major change in lysosome membrane permeation and mitochondria membrane permeation, cell cycle blockage in G2/M, and phosphatidylserine exposure. The study highlights the successful use of pequi oil nanoemulsions as delivery systems for DTX and AA, which enhances their antitumor effects against breast cancer cells. This nanotechnological approach shows significant potential for the treatment of triple-negative breast cancer.
纳米技术整合的联合疗法为乳腺癌治疗提供了一种有前景的替代方案。在纳米乳剂中加入腰果油、漆树酸（AA）和多西他赛（DTX）可以增强每个分子的抗肿瘤作用，同时减少不良反应。因此，本研究旨在开发含有DTX（PDTX）或AA（PAA）的基于腰果油的纳米乳剂（PeNE），并在体外评估它们对三阴性乳腺癌细胞（4T1）的细胞毒性。不含AA（PAA）和DTX（PDTX）的PeNE通过超声处理制备，并通过ZetaSizer和电子透射显微镜进行表征。分别采用MTT法和Chou-Talalay法测定细胞活力和联合指数（CI）。采用流式细胞术研究制剂对细胞结构的影响。PeNE、PDTX和PAA的流体动力学直径<200nm，多分散指数（PdI）为0.3。联合PDTX + PAA导致细胞活力显著下降（~70%，<0.0001）和相加效应（CI<1）。同时，DTX + AA分子的联合导致拮抗作用（CI>1）。此外，PDTX + PAA诱导了明显的形态学变化、溶酶体膜通透性和线粒体膜通透性的主要变化、细胞周期在G2/M期阻滞以及磷脂酰丝氨酸暴露。该研究突出了成功地将腰果油纳米乳剂用作DTX和AA的递送系统，增强了它们对乳腺癌细胞的抗肿瘤作用。这种纳米技术方法显示出治疗三阴性乳腺癌的巨大潜力。
