单位:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Radiol, Wuhan, Peoples R China放射科华中科技大学同济医学院附属同济医院[2]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Peoples R China中山大学附属第二医院[3]Huazhong Univ Sci & Technol, Tongji Sch Pharm, Wuhan, Peoples R China[4]Huazhong Univ Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan, Peoples R China[5]Huazhong Univ Sci & Technol, Hubei Engn Res Ctr Novel Drug Delivery Syst, Wuhan, Peoples R China
This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn2+ 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 in vitro and in vivo. 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 in vitro 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 in vitro 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 r (1) relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM(-1)center dot s(-1). 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, p=.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .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.
基金:
National Natural Science Foundation of China [82071890, 81701657, 81673374, 81872810, 81571642, 81771801]; Fundamental Research Funds for the Central Universities [2018KFYYXJJ019, 2019KFYRCPY049]; Wuhan Science and Technology Plan for Applied Fundamental Research [2017060201010146]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Radiol, Wuhan, Peoples R China
通讯作者:
通讯机构:[3]Huazhong Univ Sci & Technol, Tongji Sch Pharm, Wuhan, Peoples R China[4]Huazhong Univ Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan, Peoples R China[5]Huazhong Univ Sci & Technol, Hubei Engn Res Ctr Novel Drug Delivery Syst, Wuhan, Peoples R China
推荐引用方式(GB/T 7714):
Li Jiali,Jiang Xue,Shang Lihuan,et al.L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent[J].DRUG DELIVERY.2021,28(1):134-143.doi:10.1080/10717544.2020.1862363.
APA:
Li, Jiali,Jiang, Xue,Shang, Lihuan,Li, Zhen,Yang, Conglian...&Zhang, Zhiping.(2021).L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent.DRUG DELIVERY,28,(1)
MLA:
Li, Jiali,et al."L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent".DRUG DELIVERY 28..1(2021):134-143