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L-EGCG-Mn 纳米颗粒作为一种 pH 敏感的 MRI 对比剂。

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent.

机构信息

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Drug Deliv. 2021 Dec;28(1):134-143. doi: 10.1080/10717544.2020.1862363.

Abstract

This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both and . Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH = 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM·s. Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, =.041). The analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice ( < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.

摘要

本研究旨在合成并表征 L-表没食子儿茶素没食子酸酯(EGCG)包裹的锰纳米颗粒(L-EGCG-Mn),这是一种具有概念验证意义的 pH 敏感锰核纳米颗粒(NP),并比较其磁共振(MR)性质与 Gd-DTPA 的性质。使用反相微乳液法获得 L-EGCG-Mn NPs。使用动态光散射、透射电子显微镜和近红外荧光小动物活体成像来表征 L-EGCG-Mn 的理化性质。评估了在不同 pH 缓冲溶液(pH = 7.4、6.8、5.5)孵育的 L-EGCG-Mn 的弛豫率。使用缺氧 H22 细胞以及 H22 荷瘤小鼠评估 T1 加权磁共振成像(MRI)特性。进行细胞毒性试验和组织学分析以评估 L-EGCG-Mn 的安全性。L-EGCG-Mn 表现出良好的生物相容性、稳定性、pH 敏感性和肿瘤靶向能力。此外,当 pH 从 7.4 降低至 5.5 时,L-EGCG-Mn 的 r1 值逐渐从 1.79 增加至 6.43 mM·s。此外,在与 L-EGCG-Mn 孵育 4 小时后,缺氧 H22 细胞的 T1 弛豫时间明显低于常氧 H22 细胞(1788±89 与 1982±68 ms,=.041)。统计学分析显示,与 Gd-DTPA 相比,注射后 L-EGCG-Mn 在 H22 荷瘤小鼠中的 MRI 信号更高( < .05)。此外,通过细胞毒性试验和组织学分析发现 L-EGCG-Mn 具有良好的安全性。L-EGCG-Mn 具有良好的安全性和 pH 敏感性,因此可能成为一种有潜力的 MRI 对比剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b7d/7782420/5d26c24c723b/IDRD_A_1862363_F0001_C.jpg

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