通过叶酸修饰的脂质体纳米颗粒靶向递送奥沙利铂可增强结肠癌细胞的耐药性逆转。
Targeted delivery of oxaliplatin via folate-decorated niosomal nanoparticles potentiates resistance reversion of colon cancer cells.
发表日期:2023 Nov
作者:
Siham Abdulzehra, Davoud Jafari-Gharabaghlou, Nosratollah Zarghami
来源:
Cell Death & Disease
摘要:
结直肠癌(CRC)是一种常见的癌症,在全球发病率中排名第三,在癌症相关死亡中排名第四。年轻患者中结直肠癌相关死亡率的增加令人担忧。化疗是结肠癌姑息治疗的主要方法,但耐药性的发展限制了其有效性。细胞凋亡是一种程序性细胞死亡过程,在调节癌症中的正常细胞死亡和异常组织退化中发挥着至关重要的作用。 caspase-3、caspase-9、p53 和 survivin 等基因参与细胞凋亡诱导。纳米技术领域为控制药物输送和解决癌症耐药性提供了令人兴奋的机会。纳米体是以其令人印象深刻的特性而闻名的纳米载体之一,使其成为药物输送的绝佳候选者。在当前的研究中,我们研究了FA包被的囊泡纳米颗粒是否能够有效地将奥沙利铂递送至耐药细胞,以及结肠癌细胞中潜在的耐药性逆转。使用 DLS(动态光散射)、FTIR(傅里叶变换红外光谱)、SEM(扫描电子显微镜)和 AFM(原子力显微镜)系统进行表征。还测定了纳米颗粒的药物释放和药物封装效率。对奥沙利铂耐药细胞进行 MTT 测定,以确定纯药物和纳米胶囊形式药物的 IC50 值。使用 qRT-PCR(定量逆转录聚合酶链反应)技术研究 caspase-3、caspase-9、p53 和 survivin 的基因表达,并使用流式细胞术定量细胞凋亡或坏死。大小、PDI、zeta 电位、制备的类脂质体纳米粒子的形态、药物释放和封装效率是可接受的。奥沙利铂抗癌药物以纳米封装形式对癌细胞表现出更高的影响。 caspase-3、caspase-9 和 p53 的表达水平增加,流式细胞术结果证实了这一点。总而言之,本研究的结果证明了叶酸修饰的奥沙利铂负载的类脂质体 NP 对奥沙利铂耐药性逆转的潜在作用。结肠癌细胞耐药性。© 2023 由 Elsevier Ltd 出版。
Colorectal cancer (CRC) is a prevalent type of cancer, ranking third in incidence and fourth in cancer-related deaths globally. The increase in mortality rates related to colorectal cancer among younger patients is a cause for concern. Chemotherapy is the primary approach for palliative care in colon cancer, but the development of drug resistance limits its effectiveness. Apoptosis is a process of programmed cell death that plays a crucial role in regulating normal cell death and abnormal tissue degeneration in cancer. Genes such as caspase-3, caspase-9, p53, and survivin are involved in apoptosis induction. The field of nanotechnology has presented exciting opportunities for controlled drug delivery and addressing drug resistance in cancer. Niosomes are among the nanocarriers known for their impressive features, making them excellent candidates for drug delivery. In the current study, we investigate whether niosomal nanoparticles coated with FA have the ability to deliver oxaliplatin to drug-resistant cells effectively and potentially resistance reversion in colon cancer cells.The niosomal nanoparticles (NPs) were fabricated using the thin-film hydration method and characterized using DLS (Dynamic Light Scattering), FTIR (Fourier Transform Infrared Spectroscopy), SEM (Scanning Electron Microscopy), and AFM (Atomic Force Microscopy) systems. The drug release and drug encapsulation efficiency of the NPs were also determined. An MTT assay was performed on oxaliplatin-resistant cells to determine the IC50 values of the drug in its pure and nano-encapsulated forms. Gene expression of caspase-3, caspase-9, p53, and survivin was investigated using the qRT-PCR (quantitative Reverse Transcription Polymerase Chain Reaction) technique, and cell apoptosis or necrosis was quantified using flow cytometry.Size, PDI, zeta potential, morphology, drug release, and encapsulation efficiency of fabricated niosomal NPs were acceptable. Oxaliplatin anti-cancer drug showed a higher impact on cancerous cells in nano-encapsulated form. The expression level of caspase-3, caspase-9, and p53 was increased which was in confirmation by flow cytometry results.Taken together, results of this study demonstrated potential effect of folate decorated oxaliplatin-loaded niosomal NPs to resistance-reversion of Oxaliplatin-resistance colon cancer cells.© 2023 Published by Elsevier Ltd.