合成并验证可实现肿瘤靶向的新型磁性纳米粒子

Yingxiu Chen, Jiasheng Yan
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摘要

本研究旨在制备一种新型多功能磁性纳米粒子(MNP),该纳米粒子具有药物负载包囊和基质金属蛋白酶(MMP)底物修饰的TAT肽,其跨膜能力可在富含MMP的环境中被激活,并评估细胞对这种纳米粒子的吸收及其细胞毒性。研究人员合成了纳米颗粒,并用 TAT 或 MMPs-TAT 肽对其进行修饰。PC-3 细胞和 RWPE-1 细胞在有或没有 MMP-2 预处理的情况下培养了不同浓度的纳米颗粒,并使用流式细胞仪和荧光显微镜测定了它们的吸收率和毒性。用 TEM(透射电子显微镜)和 DLS(动态光散射)对纳米颗粒进行了表征。这些纳米颗粒的直径在 194.5 ± 69.4 nm 到 353.1 ± 103.9 nm 之间,处于理想的应用范围。细胞对 MMPs-TAT-MNPs 的吸收与 MNPs 相似,但在 MMP-2 预处理的情况下会显著增加。MMPs-TAT-MNPs 在浓度≤25 μg/ml 时没有明显的细胞毒性。含 MMP-2 底物修饰 TAT 肽的 MMPs-TAT-MNPs 制备成功,具有低细胞毒性的可负载货物,并可在富含 MMP-2 的生态位中激活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and Verification of a Novel Attainable Tumor Targeting Magnetic Nanoparticle
This study aimed to prepare a novel multifunctional magnetic nanoparticle (MNP) with a drug-loadable encapsulation and a matrix metalloproteinase (MMP) substrate-modified TAT peptide whose transmembrane ability can be activated in an MMP-rich environment, and to evaluate the uptake of this nanoparticle by cells, as well as its cytotoxicity. Nanoparticles were synthesized and modified with TAT or MMPs-TAT peptides. PC-3 cells and RWPE-1 cells were cultured with these nanoparticles at different concentrations, with or without MMP-2 pretreatment, and their uptake rate and toxicity were determined using flow cytometry and fluorescence microscopy. The nanoparticles were characterized with TEM (transmission electron microscopy) and DLS (dynamic light scattering). The diameter of these nanoparticles ranged from 194.5 ± 69.4 nm to 353.1 ± 103.9 nm, which were in the ideal range for application. The cellular uptake of MMPs-TAT-MNPs appeared similar to MNPs, but significantly increased in the presence of MMP-2 pretreatment. MMPs-TAT-MNPs had no significant cytotoxicity at the concentration of ≤25 μg/ml. MMPs-TAT-MNPs with MMP-2 substrate modified TAT peptide is successfully prepared, possess a low cytotoxicity loadable cargo and can be activated in an MMP-2 rich niche.
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