Department of Chemistry, Federal University of Pernambuco, Recife 50670-901, PE, Brazil.
School of Biomedical Sciences, Departments of Microbiology, Immunology, and Genetics and Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Int J Mol Sci. 2024 Jul 25;25(15):8097. doi: 10.3390/ijms25158097.
Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH-DTPA-Gd⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC concentration of 12.6 mg/mL compared to an EC concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH-DTPA-Gd⁺-MIH and its potential to enhance breast cancer management.
晚期乳腺癌仍然是一个重大的肿瘤学挑战,需要新的方法来改善临床结果。本研究利用 MCM-41-NH-DTPA-Gd⁺-MIH 纳米材料研究了一种创新的治疗诊断一体化试剂,该纳米材料将 MRI 成像用于检测和新型化疗药物(MIH 2.4Bl)用于治疗相结合。纳米材料基于介孔硅类型的 MCM-41,通过功能化胺基、与 DTPA 缀合以及与 Gd 络合进行药物传递进行了优化。使用基于钆的对比剂增强了 MRI 敏感性,这对于识别早期肿瘤病变至关重要。MIH 2.4Bl 具有独特的介离子结构,允许与生物分子有效相互作用,从而促进其细胞内抗肿瘤活性。物理化学特性表征证实了纳米材料的合成和有效药物结合,其中 15%的 MIH 2.4Bl 被吸附。药物释放试验表明,大约 50%的药物在 8 小时内释放。MRI 体模研究表明,该纳米材料具有优异的成像能力,弛豫率明显高于商用试剂 Magnevist。体外细胞毒性试验表明,与正常的人乳腺上皮细胞(HMECs)相比,该纳米材料在杀死 MDA-MB-231 乳腺癌细胞方面的有效浓度(EC)为 12.6mg/mL,而在正常的人乳腺上皮细胞(HMECs)中则为 68.9mg/mL。在体内,在 4T1 同源小鼠模型中进行的 MRI 评估证实了其作为造影剂的功效。本研究强调了 MCM-41-NH-DTPA-Gd⁺-MIH 的治疗诊断一体化能力及其增强乳腺癌管理的潜力。