Department of Molecular and cell Biology, Faculty of Basic Sciences, University of Mazandaran, 47416-95447, Babolsar, Iran.
Department of Life Science Engineering, Faculty of New Sciences and Technology, University of Tehran, Tehran, Iran.
Chem Biodivers. 2023 Sep;20(9):e202300659. doi: 10.1002/cbdv.202300659. Epub 2023 Sep 5.
Breast cancer is a malignancy that affects mostly females and is among the most lethal types of cancer. The ligand-functionalized nanoparticles used in the nano-drug delivery system offer enormous potential for cancer treatments. This work devised a promising approach to increase drug loading efficacy and produce sustained release of 5-fluorouracil (5-FU) and Ganoderic acid (GA) as model drugs for breast cancer. Chitosan, aptamer, and carbon quantum dot (CS/Apt/COQ) hydrogels were initially synthesized as a pH-sensitive and biocompatible delivery system. Then, CS/Apt/COQ NPs loaded with 5-FU-GA were made using the W/O/W emulsification method. FT-IR, XRD, DLS, zeta potentiometer, and SEM were used to analyze NP's chemical structure, particle size, and shape. Cell viability was measured using MTT assays in vitro using the MCF-7 cell lines. Real-time PCR measured cell apoptotic gene expression. XRD and FT-IR investigations validated nanocarrier production and revealed their crystalline structure and molecular interactions. DLS showed that nanocarriers include NPs with an average size of 250.6 nm and PDI of 0.057. SEM showed their spherical form, and zeta potential studies showed an average surface charge of +37.8 mV. pH 5.4 had a highly effective and prolonged drug release profile, releasing virtually all 5-FU and GA in 48 h. Entrapment efficiency percentages for 5-FU and GA were 84.7±5.2 and 80.2 %±2.3, respectively. The 5-FU-GA-CS-CQD-Apt group induced the highest cell death, with just 57.9 % of the MCF-7 cells surviving following treatment. 5-FU and GA in CS-CQD-Apt enhanced apoptotic induction by flow cytometry. 5-FU-GA-CS-CQD-Apt also elevated Caspase 9 and downregulated Bcl2. Accordingly, the produced NPs may serve as pH-sensitive nano vehicles for the controlled release of 5-FU and GA in treating breast cancer.
乳腺癌是一种主要影响女性的恶性肿瘤,也是最致命的癌症类型之一。在纳米药物递送系统中使用配体功能化的纳米粒子为癌症治疗提供了巨大的潜力。本工作设计了一种有前途的方法来提高药物负载效率,并产生 5-氟尿嘧啶(5-FU)和灵芝酸(GA)的持续释放,作为乳腺癌的模型药物。壳聚糖、适体和碳量子点(CS/Apt/COQ)水凝胶最初被合成作为一种 pH 敏感和生物相容的递送系统。然后,使用 W/O/W 乳化法制备负载 5-FU-GA 的 CS/Apt/COQ NPs。FT-IR、XRD、DLS、zeta 电位计和 SEM 用于分析 NP 的化学结构、粒径和形状。使用 MCF-7 细胞系通过 MTT 测定法在体外测量细胞活力。实时 PCR 测量细胞凋亡基因表达。XRD 和 FT-IR 研究验证了纳米载体的生产,并揭示了它们的晶体结构和分子相互作用。DLS 表明纳米载体包含平均粒径为 250.6nm 和 PDI 为 0.057 的 NPs。SEM 显示其球形形态,zeta 电位研究显示平均表面电荷为+37.8mV。在 pH 5.4 时,具有高效和持久的药物释放特性,在 48 小时内几乎释放所有的 5-FU 和 GA。5-FU 和 GA 的包封效率百分比分别为 84.7±5.2 和 80.2±2.3。5-FU-GA-CS-CQD-Apt 组诱导细胞死亡最高,经处理后仅有 57.9%的 MCF-7 细胞存活。5-FU 和 GA 在 CS-CQD-Apt 中通过流式细胞术增强了诱导凋亡。5-FU-GA-CS-CQD-Apt 还升高了 Caspase 9 并下调了 Bcl2。因此,所制备的 NPs 可作为 pH 敏感的纳米载体,用于控制 5-FU 和 GA 在治疗乳腺癌中的释放。