School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People's Republic of China.
State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu, 611137, People's Republic of China.
Int J Nanomedicine. 2021 Mar 29;16:2487-2499. doi: 10.2147/IJN.S294279. eCollection 2021.
Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer.
In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity.
Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions.
SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles' self-monitoring function has been developed, opening up new ideas for combined tumor therapy.
由于纳米载体的缺点，载体无纳米递药系统的开发在癌症治疗中越来越受到关注。然而，很少有研究关注能够同时实现监测功能的无载体纳米系统。在这里，我们建立了一种载有姜黄素和盐酸伊立替康的多功能无载体纳米系统，用于胃癌的治疗和监测。
在这项研究中，我们制备了一种盐酸伊立替康-姜黄素纳米系统（命名为 SICN）。基于姜黄素的荧光，我们使用流式细胞术、激光共聚焦显微镜和斑马鱼荧光成像来研究 SICN 在体内和体外的监测功能。此外，我们用人胃癌 HGC-27 细胞来研究 SICN 的细胞毒性。
流式细胞术和斑马鱼荧光成像监测结果表明，SICN 的摄取明显高于游离姜黄素，且排泄率较低。SICN 在细胞和斑马鱼中的积累和保留更高。激光共聚焦显微镜监测结果表明，SICN 通过多种途径被内化进入 HGC-27 细胞，包括巨胞饮、小窝蛋白、网格蛋白介导和网格蛋白非依赖的内吞作用，并且分布在整个细胞质内，包括溶酶体和高尔基体。体外细胞实验表明，SICN 纳米颗粒比单一成分更具毒性，并且在略酸性条件下，HGC-27 细胞对纳米颗粒的吸收更多，毒性更高。
SICN 是一种很有前途的无载体纳米颗粒，两种单一组分疗法的联合可以发挥协同抗肿瘤作用。当暴露于肿瘤酸性环境时，由于电荷转换，SICN 表现出更强的细胞毒性。更重要的是，纳米颗粒的自我监测功能已经得到开发，为联合肿瘤治疗开辟了新的思路。
