Elfiky Asmaa M, Eid May M, El-Manawaty May, Elshahid Zeinab A, Youssef Elham Mohamed, Mahmoud Khaled
Environmental and Occupational Medicine Department, Environment and Climate Change Research Institute, National Research Centre, Cairo, Egypt.
Physics Institute, National Research Center, Dokki, Cairo, Egypt.
Sci Rep. 2025 Feb 4;15(1):4247. doi: 10.1038/s41598-025-88165-3.
Colorectal cancer (CRC) is a serious public health concern worldwide. Immune checkpoint inhibition medication is likely to remain a crucial part of CRC clinical management. This study aims to create new super paramagnetic iron oxide nano-carrier (SPION) that can effectively transport miRNA to specific CRC cell lines. In addition, evaluate the efficiency of this nano-formulation as a therapeutic candidate for CRC. Bioinformatics tools were used to select a promising tumor suppressor miRNA (mir-497-5p). Green route, using Fusarium oxyporium fungal species, manipulated for the synthesis of SPION@Ag@Cs nanocomposite as a carrier of miR-497-5p. That specifically targets the suppression of PD1/PDL1 and CTLA4pathways for colorectal therapy. UV/visible and FTIR spectroscopy, Zeta potential and MTT were used to confirm the allocation of the miR-497 on SPION@Ag@Cs and its cytotoxicity against CRC cell lines. Immunofluorescence was employed to confirm transfection of cells with miR-497@NPs, and the down- regulation of CTLA4 in HT29, and Caco2 cell lines. On the other hand, PDL1 showed a significant increase in colorectal cell lines (HT-29 and Caco-2) in response to mir497-5p@Nano treatment. The data suggest that the mir-497 -loaded SPION@Ag@Cs nano-formulation could be a good candidate for the suppression of CTLA4in CRC human cell lines. Consequently, the targeting miR-497/CTLA4 axis is a potential immunotherapy treatment strategy for CRC.
结直肠癌(CRC)是全球严重的公共卫生问题。免疫检查点抑制药物可能仍将是CRC临床管理的关键部分。本研究旨在创建新型超顺磁性氧化铁纳米载体(SPION),其能够有效地将微小RNA转运至特定的CRC细胞系。此外,评估这种纳米制剂作为CRC治疗候选物的效率。使用生物信息学工具来选择一种有前景的肿瘤抑制性微小RNA(mir-497-5p)。采用绿色路线,利用尖孢镰刀菌合成作为miR-497-5p载体的SPION@Ag@Cs纳米复合材料。其特异性靶向抑制用于结直肠癌治疗的PD1/PDL1和CTLA4信号通路。使用紫外/可见光谱和傅里叶变换红外光谱、zeta电位和MTT法来确认miR-497在SPION@Ag@Cs上的负载情况及其对CRC细胞系的细胞毒性。采用免疫荧光法来确认细胞被miR-497@NPs转染,以及HT29和Caco2细胞系中CTLA4的下调情况。另一方面,在对mir497-5p@Nano治疗的反应中,结直肠癌细胞系(HT-29和Caco-2)中的PDL1显著增加。数据表明,负载mir-497的SPION@Ag@Cs纳米制剂可能是CRC人细胞系中抑制CTLA4的良好候选物。因此,靶向miR-497/CTLA4轴是CRC潜在的免疫治疗策略。