Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, 563000, People's Republic of China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, People's Republic of China.
Int J Nanomedicine. 2023 Mar 21;18:1347-1362. doi: 10.2147/IJN.S399568. eCollection 2023.
Radiotherapy and chemotherapy are the fundamental causes of myelosuppression in cancer patients, which usually induce a serious hematopoietic system toxicity, causing the hemocytes and immunity decline of patients. Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells, which is related to its promotion of autophagy in hematopoietic stem cells.
In the present study, we formulated the SH-PEG-NH-coated gold nanoparticles loading ZgI (ZgI-AuNPs) with a enhanced autophagy promotion in hematopoietic stem cells. ZgI-AuNPs were prepared by HAuCl-sodium citrate reduction method, and the synthesis of ZgI-AuNPs was validated by XRD, FT-IR, DSC, and TEM findings. Furthermore, the drug loading rate and the release of ZgI were evaluated, and the ZgI-AuNPs' effects on autophagy and immunofluorescence staining for LC3B were tested. Finally, the effect of ZgI-AuNPs on the autophagy and hematopoietic ability of HSCs in vivo was also carried out.
The prepared ZgI-AuNPs have an irregular cubic crystal structure by TEM observation, and the average particle size was 340 ± 16.5 nm determined by DLS. The XRD, FT-IR and DSC detection showed that the ZgI had been well loaded in AuNPs, and the AuNPs can load the ZgI at a content of 160.63 ± 1.35 μg·mg. Meanwhile, the AuNPs can reduce the drug release rate of ZgI. Importantly, the ZgI-AuNPs enhanced autophagy of HSCs both in vitro and in vivo. At the same time, the gold nanoparticles enhance the hematopoietic effect of ZgI on mice HSCs.
Our research suggests that SH-PEG-NH-coated gold nanoparticles loading ZgI has potential application in myelosuppression therapy.
放射治疗和化学疗法是癌症患者骨髓抑制的根本原因，通常会导致严重的造血系统毒性，使患者的血细胞和免疫力下降。从中药 L 中分离得到的活性成分梓醇苷 I（ZgI）已被证明可增加白细胞并保护造血干细胞，这与其促进造血干细胞自噬有关。
在本研究中，我们通过 SH-PEG-NH 涂层金纳米粒子负载 ZgI（ZgI-AuNPs）来增强造血干细胞中的自噬作用。ZgI-AuNPs 通过 HAuCl-柠檬酸钠还原法制备，并通过 XRD、FT-IR、DSC 和 TEM 结果验证了 ZgI-AuNPs 的合成。此外，评估了 ZgI 的载药量和释放情况，并测试了 ZgI-AuNPs 对自噬和 LC3B 免疫荧光染色的影响。最后，还进行了 ZgI-AuNPs 对体内 HSCs 自噬和造血能力的影响。
通过 TEM 观察，制备的 ZgI-AuNPs 具有不规则立方晶相结构，通过 DLS 测定平均粒径为 340±16.5nm。XRD、FT-IR 和 DSC 检测表明，ZgI 已很好地负载在 AuNPs 中，AuNPs 可将 ZgI 的载药量装载至 160.63±1.35μg·mg。同时，AuNPs 可以降低 ZgI 的药物释放率。重要的是，ZgI-AuNPs 增强了 HSCs 的自噬作用，无论是在体外还是体内。同时，金纳米粒子增强了 ZgI 对小鼠 HSCs 的造血作用。
我们的研究表明，SH-PEG-NH 涂层金纳米粒子负载 ZgI 具有治疗骨髓抑制的潜在应用价值。
