Targeted Delivery of Pennyroyal via Methotrexate Functionalized PEGylated Nanostructured Lipid Carriers into Breast Cancer Cells; A Multiple Pathways Apoptosis Activator.

IF 3.1 Q2 PHARMACOLOGY & PHARMACY Advanced pharmaceutical bulletin Pub Date : 2023-11-01 Epub Date: 2023-04-29 DOI:10.34172/apb.2023.077

Amin Mahoutforoush, Leila Asadollahi, Hamed Hamishehkar, Soheil Abbaspour-Ravasjani, Atefeh Solouk, Masoumeh Haghbin Nazarpak

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Abstract

Purpose: Pennyroyal is a species of the Lamiaceae family with potent anti-cancer and antioxidant properties. Combining this antioxidant with chemotherapeutic agents enhances the effectiveness of these agents by inducing more apoptosis in cancerous cells.

Methods: Here, methotrexate (MTX) combined with pennyroyal oil based on PEGylated nanostructured lipid carriers (NLCs) was assessed. These nanoparticles were physiochemically characterized, and their anti-cancer effects and targeting efficiency were investigated on the folate receptor-positive human breast cancer cell line (MCF-7) and negative human alveolar basal epithelial cells (A549).

Results: Results showed a mean size of 97.4 ± 12.1 nm for non-targeted PEGylated NLCs and 220.4 ± 11.4 nm for targeted PEGylated NLCs, with an almost small size distribution assessed by TEM imaging. Furthermore, in vitro molecular anti-cancer activity investigations showed that pennyroyal-NLCs and pennyroyal-NLCs/MTX activate the apoptosis and autophagy pathway by changing their related mRNA expression levels. Furthermore, in vitro cellular studies showed that these changes in the level of gene expression could lead to a rise in apoptosis rate from 15.6 ± 8.1 to 25.0 ± 3.2 (P<0.05) for the MCF-7 cells treated with pennyroyal-NLCs and pennyroyal-NLCs/MTX, respectively. Autophagy and reactive oxygen species (ROS) cellular evaluation indicated that treating the cells with pennyroyal-NLCs and pennyroyal-NLCs/MTX could significantly increase their intensity in these cells.

Conclusion: Our results present a new NLCs-based approach to enhance the delivery of pennyroyal and MTX to cancerous breast tissues.

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通过甲氨蝶呤功能化聚乙二醇化纳米结构脂质载体将Pennyroyal靶向递送到乳腺癌症细胞中；一种多途径细胞凋亡激活剂

目的：Pennyroyal是Lamiaceae科的一种，具有强大的抗癌和抗氧化特性。将这种抗氧化剂与化学治疗剂结合，通过诱导癌细胞更多的凋亡来增强这些药物的有效性。方法：以聚乙二醇化纳米结构脂质载体（NLCs）为基础，对甲氨蝶呤（MTX）与Pennyroyal油联合应用进行评价。对这些纳米颗粒进行了理化表征，并对其在叶酸受体阳性的人乳腺癌症细胞系（MCF-7）和阴性的人肺泡基底上皮细胞（A549）上的抗癌作用和靶向效率进行了研究。结果：结果显示，非靶向PEG化的NLCs的平均尺寸为97.4±12.1nm，靶向PEG性的NLCs为220.4±11.4nm，TEM成像评估的尺寸分布几乎很小。此外，体外分子抗癌活性研究表明，Pennyroyal-NLCs和Pennyroyal-NLCs/MTX通过改变其相关mRNA表达水平来激活细胞凋亡和自噬途径。此外，体外细胞研究表明，基因表达水平的这些变化可导致用Pennyroyal NLCs和Pennyroyl NLC/MTX处理的MCF-7细胞的凋亡率分别从15.6±8.1上升到25.0±3.2（p<0.05）。自噬和活性氧细胞评估表明，用Pennyroyal NLCs和Pennyroyl NLCs/MTX处理细胞可以显著增加它们在这些细胞中的强度。结论：我们的研究结果提供了一种新的基于NLCs的方法来增强Pennyroyal和MTX对癌性乳腺组织的递送。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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