研究动态
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多功能 β-环糊精包覆 Bi2O3 纳米粒子与姜黄素结合用于 CT 成像引导的乳腺癌协同放化疗的表征。

Characterization of multifunctional β-cyclodextrin-coated Bi2O3 nanoparticles conjugated with curcumin for CT imaging-guided synergetic chemo-radiotherapy in breast cancer.

发表日期:2024 May 22
作者: Maedeh Yektamanesh, Yasin Ayyami, Marjan Ghorbani, Masoumeh Dastgir, Reza Malekzadeh, Tohid Mortezazadeh
来源: INTERNATIONAL JOURNAL OF PHARMACEUTICS

摘要:

基于纳米技术的诊断和治疗方法彻底改变了癌症检测和治疗领域,为疾病早期阶段的经济有效的干预措施提供了巨大的潜力。本研究合成了氧化铋 (Bi2O3) 纳米颗粒 (NP),该纳米颗粒经聚环糊精 (PCD) 修饰,并用葡萄糖 (Glu) 功能化以负载姜黄素 (CUR),用于乳腺癌的 CT 成像和放化疗应用。制备的Bi2O3@PCD-CUR-Glu NPs进行了全面的表征,涵盖细胞迁移、细胞毒性、细胞摄取、血液相容性、活性氧(ROS)生成能力、实时PCR分析、体内安全性评估等多个方面、体内抗肿瘤功效,以及体外CT对比和X线RT增强评价。在静脉注射 Bi2O3@PCD-CUR-Glu NPs 之前和之后(1 和 3 小时)进行 CT 扫描。通过使用耦合等离子体发射光谱 (ICP-OES) 分析,评估了最终制备的纳米粒子在 Bab/c 小鼠中的分布。最终合成的直径约为 80 nm 的球形纳米粒子对 SKBr-3 乳腺癌细胞系表现出异常的毒性。在100μg/mL浓度、2Gy辐射剂量下暴露48小时后,细胞活力达到最低水平。使用 Bi2O3@PCD-CUR-Glu NP 和 X 射线辐射的联合治疗显示 ROS 的产生显着增加,特别是显着增加了 420%。基因表达分析表明P53和BAX促凋亡基因的表达水平显着增加。体外 CT 成像分析明确证明了 NP 在 X 射线吸收能力方面比 Omnipaque 具有显着优势,在 80 kVp 时增加了惊人的 1.52 倍。结果表明,靶向 Bi2O3@PCD-CUR-Glu NP 可以增强小小鼠肿瘤的可见度,该肿瘤可通过计算机断层扫描检测到,并通过 X 射线衰减变得可见。结果表明,Bi2O3@PCD-CUR-Glu NPs 与 CT 成像和放化疗相结合,具有作为临床应用的多功能治疗诊断系统的巨大潜力。版权所有 © 2024。由 Elsevier B.V. 出版。
Nanotechnology-based diagnostic, and therapeutic approaches revolutionized the field of cancer detection, and treatment, offering tremendous potential for cost-effective interventions in the early stages of disease. This research synthesized bismuth oxide (Bi2O3) nanoparticles (NPs) that were modified with polycyclodextrin (PCD), and functionalized with glucose (Glu) to load curcumin (CUR) for CT imaging and chemo-radiotherapy applications in Breast Cancer. The prepared Bi2O3@PCD-CUR-Glu NPs underwent comprehensive characterization, encompassing various aspects, including cell migration, cytotoxicity, cellular uptake, blood compatibility, reactive oxygen species (ROS) generation ability, real-time PCR analysis, in-vivo safety assessment, in-vivo anti-tumor efficacy, as well as in-vitro CT contrast and X-ray RT enhancement evaluation. CT scan was conducted before and after (1 and 3 h) intravenous injection of Bi2O3@PCD-CUR-Glu NPs. Through the use of coupled plasma optical emission spectrometry (ICP-OES) analysis, the final prepared nanoparticle distribution in the Bab/c mice was assessed. The spherical NPs that were ultimately synthesized and had a diameter of around 80 nm demonstrated exceptional toxicity towards the SKBr-3 breast cancer cell line. The cell viability was at its lowest level after 48 h of exposure to a radiation dose of 2 Gy at a concentration of 100 µg/mL. The combined treatment involving using Bi2O3@PCD-CUR-Glu NPs along with X-ray radiation showed a substantial increase in the generation of ROS, specifically a remarkable 420 % growth. Gene expression analysis indicated that the expression levels of P53, and BAX pro-apoptotic genes were significantly increased. The in-vitro CT imaging analysis conducted unequivocally demonstrated the notable superiority of NPs over Omnipaque in terms of X-ray absorption capacity, a staggering 1.52-fold increase at 80 kVp. The resultsdemonstrated that the targeted Bi2O3@PCD-CUR-Glu NPs could enhance the visibility of a small mice tumor that is detectable by computed tomography and made visible through X-ray attenuation. Results suggested that Bi2O3@PCD-CUR-Glu NPs, integrated with CT imaging and chemo-radiotherapy, have great potential as a versatile theranostic system for clinical application.Copyright © 2024. Published by Elsevier B.V.