FRET-based intracellular investigation of nanoprodrugs toward highly efficient anticancer drug delivery
FRET-based intracellular investigation of nanoprodrugs toward highly efficient anticancer drug delivery
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基于 FRET 的纳米前药细胞内研究以实现高效抗癌药物递送
DOI：
10.1039/d0nr04910g
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发表时间：
2020
期刊：
影响因子：
6.7
通讯作者：
Kasai Hitoshi
中科院分区：
文献类型：
--
作者：
Taemaitree Farsai;Fortuni Beatrice;Koseki Yoshitaka;Fron Eduard;Rocha Susana;Hofkens Johan;Uji-i Hiroshi;Inose Tomoko;Kasai Hitoshi
为了克服传统的基于载体的抗癌药物递送系统的不可预测的副作用和增加的细胞毒性，已经提出了几种仅由纯药物（或前药）组成的系统。然而，这些系统进入癌细胞后的行为和动力学仍然是未知的，阻碍了它们在体内和临床应用方面的进展。在这里，我们报告了一项全面的无载体SN-38纳米前药（NPD）的细胞研究，该研究是我们小组以前开发的。这项工作显示了细胞内的摄取，定位和降解的NPD通过FRET显微镜。因此，化学合成并表征了新的FRET-NPD。还验证了前药至药物的转化和治疗效率。我们的工作为NPD作为药物递送系统的应用提供了重要信息，并展示了其作为下一代抗癌纳米药物的杰出潜力。
In order to overcome unpredictable side-effects and increased cytotoxicity of conventional carrier-based anticancer drug delivery systems, several systems that consist exclusively of the pure drug (or prodrug) have been proposed. The behavior and dynamics of these systems after entering cancer cells are, however, still unknown, hindering their progress towards in vivo and clinical applications. Here, we report a comprehensive in cellulo study of carrier-free SN-38 nanoprodrugs (NPDs), previously developed by our group. The work shows the intracellular uptake, localization, and degradation of the NPDs via FRET microscopy. Accordingly, new FRET-NPDs were chemically synthesized and characterized. Prodrug to drug conversion and therapeutic efficiency were also validated. Our work provides crucial information for the application of NPDs as drug delivery systems and demonstrates their outstanding potential as next-generation anticancer nanomedicines.