Afereydoon Saeid, Haghiralsadat Fateme, Hamzian Nima, Shams Ali, Hemati Mahdie, Naghib Seyed Morteza, Shabani Masoud, Zandieh-Doulabi Behrouz, Tofighi Davood
Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Front Bioeng Biotechnol. 2022 Aug 15;10:917368. doi: 10.3389/fbioe.2022.917368. eCollection 2022.
Nowadays, radiotherapy is one of the most effective treatments for breast cancer. In order to overcome the radioresistance of cancer cells, radio-sensitizing agents can be used combined with irradiation to increase the therapeutic efficiency. Curcumin can enhance the radiosensitivity of cancer cells and decrease their viability by the accumulation of these cells in the G2 phase. The encapsulation of curcumin in a nanoniosomal delivery system increases aqueous solubility and bioavailability, resulting in increased radio sensitivity. The present study aimed to enhance the radio-sensitizing effect of the curcumin-containing nanoniosome (Cur-Nio) when combined with irradiation. Thus, curcumin (0.5 mg ml) was loaded on a PEGylated nanoniosome containing Tween 60, cholesterol, DOTAP, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (at ratios of 70:30:10:5, respectively) by the thin-film hydration method. The particle size, zeta potential, entrapment efficiency, and drug-release rate of formulated nanoniosomes were determined. In order to assess cytotoxicity and apoptosis, different doses of irradiation along with various concentrations of free curcumin and Cur-Nio (single or in combination with irradiation) were treated with breast cancer cells. The particle size and zeta potential of Cur-Nio were reported to be 117.5 nm and -15.1 mV, respectively. The entrapment efficiency (EE%) and loading capacities were 72.3% and 6.68%, respectively. The drug-release rate during 6 h was 65.9%. Cell survival in the presence of curcumin at doses of 1 and 3 Gy showed a significant reduction compared with cells irradiated at 48 h and 72 h ( < 0.000). Also, the rate of cytotoxicity and apoptosis was significantly higher in cells treated with the combination of curcumin-containing nanoniosomes and irradiation in comparison with those treated with free curcumin. These findings indicate that the efficacy of pre-treatment with Cur-Nio as a radiosensitizer during radiotherapy enhances irradiation-induced breast cancer cell apoptosis and is a useful strategy to increase the effectiveness of breast cancer therapy.
如今，放射治疗是乳腺癌最有效的治疗方法之一。为了克服癌细胞的放射抗性，可将放射增敏剂与照射联合使用以提高治疗效果。姜黄素可增强癌细胞的放射敏感性，并通过使这些细胞在G2期积累来降低其活力。将姜黄素包裹在纳米非离子体递送系统中可提高其水溶性和生物利用度，从而提高放射敏感性。本研究旨在增强含姜黄素纳米非离子体（Cur-Nio）与照射联合使用时的放射增敏效果。因此，采用薄膜水化法将姜黄素（0.5 mg/ml）负载于含有吐温60、胆固醇、DOTAP和1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-聚（乙二醇）（DSPE-PEG）（比例分别为70:30:10:5）的聚乙二醇化纳米非离子体上。测定了所制备纳米非离子体的粒径、zeta电位、包封率和药物释放率。为了评估细胞毒性和细胞凋亡，用不同剂量的照射以及不同浓度的游离姜黄素和Cur-Nio（单独或与照射联合）处理乳腺癌细胞。据报道，Cur-Nio的粒径和zeta电位分别为117.5 nm和 -15.1 mV。包封率（EE%）和载药量分别为72.3%和6.68%。6小时内的药物释放率为65.9%。与在48小时和72小时照射的细胞相比，在1 Gy和3 Gy剂量的姜黄素存在下细胞存活率显著降低（<0.000）。此外，与用游离姜黄素处理的细胞相比，用含姜黄素纳米非离子体与照射联合处理的细胞的细胞毒性和细胞凋亡率显著更高。这些发现表明，在放射治疗期间用Cur-Nio作为放射增敏剂进行预处理可增强照射诱导的乳腺癌细胞凋亡，是提高乳腺癌治疗效果的一种有用策略。
