Zargarani Nadia, Kavousi Mahsa, Aliasgari Elahe
Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran.
BMC Cancer. 2025 May 12;25(1):860. doi: 10.1186/s12885-025-14249-y.
Solanine has been shown to inhibit cancer by regulating the expression of apoptosis (Bax, Bcl-2) and metastasis (CDH-1, MMP2) genes in various cancer cell types. We synthesized optimized niosome NPs (NPs) with high solubility and capacity for solanine loading. In this study, the cytotoxic, cell cycle inhibitory and apoptotic effects of solanine-loaded niosome NPs (SN-NPs) on MCF-7 were investigated. Thin-layer hydration was used to generate SN-NPs and their features were validated. The pH-dependent solanine release pattern was also examined. Synthesized SN-NPs were evaluated for cytotoxicity against MCF-7 and MCF-10 cell lines using MTT. Primary and secondary apoptosis, necrosis, and cell cycle arrest were measured using flowcytometry. Lastly, q-PCR was used to assess the expression of genes. The NPs had an average size between 50 and 70 nm, with a polydispersity index (PDI) of 0.452. Solanine was effectively incorporated into noisome NPs, as shown by the high encapsulation efficiency of 82.3%±0.24%. After a quick burst at pH 7 and 5, SN-NPs released slowly and sustainedly. The IC of solanine-loaded niosomes against MCF-7 cells decreased from 40 mg/100 mL to 10 mg/100 mL (48 h) and 5 mg/100 mL (72 h). After 72 h, SN-NPs caused late apoptosis in 30% of MCF-7 cells and necrosis in 5.06% (p < 0.01). SN-NPs caused 81% of cells to arrest in the G0/G1 phase, with only 12% progressing to G2/M (p < 0.01). Solanine-loaded NPs significantly increased Bax and CDH-1 gene expression in malignant cells compared to free niosomes and free solanine (p < 0.0001). Bcl-2 and MMP2 expression significantly decreased in this group compared to free niosomes and free solanine (p < 0.001). Solanine-containing niosomes showed significant anticancer effects on MCF-7 breast cancer cells, which were supported by apoptosis, cell cycle arrest and regulation of gene expression. The regulated release and precise delivery of solanine using SN-NPs show considerable translational potential. This improved nanocarrier technology may increase the bioavailability and efficacy of solanine, potentially leading to improved clinical outcomes in breast cancer therapy.
茄碱已被证明可通过调节多种癌细胞类型中凋亡(Bax、Bcl - 2)和转移(CDH - 1、MMP2)基因的表达来抑制癌症。我们合成了具有高溶解度和茄碱负载能力的优化脂质体纳米颗粒(NPs)。在本研究中,研究了负载茄碱的脂质体纳米颗粒(SN - NPs)对MCF - 7细胞的细胞毒性、细胞周期抑制和凋亡作用。采用薄膜水化法制备SN - NPs并验证其特性。还检测了pH依赖性的茄碱释放模式。使用MTT法评估合成的SN - NPs对MCF - 7和MCF - 10细胞系的细胞毒性。通过流式细胞术测量原发性和继发性凋亡、坏死以及细胞周期停滞。最后,使用q - PCR评估基因表达。这些纳米颗粒的平均粒径在50至70nm之间,多分散指数(PDI)为0.452。茄碱有效负载于脂质体纳米颗粒中,包封率高达82.3%±0.24%。在pH 7和5时快速释放一阵后,SN - NPs缓慢且持续释放。负载茄碱的脂质体对MCF - 7细胞的半数抑制浓度(IC)在48小时时从40mg/100mL降至10mg/100mL,72小时时降至5mg/100mL。72小时后,SN - NPs导致30%的MCF - 7细胞发生晚期凋亡,5.06%发生坏死(p < 0.01)。SN - NPs使81%的细胞停滞在G0/G1期,仅有12%进入G2/M期(p < 0.01)。与游离脂质体和游离茄碱相比,负载茄碱的纳米颗粒显著增加了恶性细胞中Bax和CDH - 1基因的表达(p < 0.0001)。与游离脂质体和游离茄碱相比,该组中Bcl - 2和MMP2的表达显著降低(p < 0.001)。含茄碱的脂质体对MCF - 7乳腺癌细胞显示出显著的抗癌作用,这得到了凋亡、细胞周期停滞和基因表达调控的支持。使用SN - NPs对茄碱进行控释和精准递送显示出相当大的转化潜力。这种改进的纳米载体技术可能会提高茄碱的生物利用度和疗效,有望改善乳腺癌治疗的临床结果。