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负载人参皂苷Compound K的离子交联羧甲基壳聚糖-钙纳米粒的表征及其对前列腺癌细胞的细胞毒性潜力

Characterization of ginsenoside compound K loaded ionically cross-linked carboxymethyl chitosan-calcium nanoparticles and its cytotoxic potential against prostate cancer cells.

作者信息

Zhang Jianmei, Zhou Jinyi, Yuan Qiaoyun, Zhan Changyi, Shang Zhi, Gu Qian, Zhang Ji, Fu Guangbo, Hu Weicheng

机构信息

Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian 223300, China.

Department of Urology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, 223300, China.

出版信息

J Ginseng Res. 2021 Mar;45(2):228-235. doi: 10.1016/j.jgr.2020.01.007. Epub 2020 Feb 5.

DOI:10.1016/j.jgr.2020.01.007
PMID:33841003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8020349/
Abstract

BACKGROUD

Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities and . This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK-OCMC Nps), which enhance the aqueous solubility and stability of GK.

METHODS

The GK-OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK-OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK-OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK-OCMC Nps.

RESULTS

The GK-OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. drug release from GK-OCMC NPs was pH dependent. Moreover, the cytotoxicity study and cellular uptake assays indicated that the GK-OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK-OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9.

CONCLUSION

GK-OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

摘要

背景

人参皂苷Compound K（GK）是原人参二醇型人参皂苷的主要代谢产物，具有显著的抗癌活性。本研究采用离子交联法将GK包裹于O-羧甲基壳聚糖（OCMC）纳米粒（Nps）中，形成载GK的OCMC纳米粒（GK-OCMC Nps），以提高GK的水溶性和稳定性。

方法

采用多种物理化学技术对GK-OCMC Nps进行表征，包括X射线衍射、透射电子显微镜、zeta电位分析以及通过动态光散射进行粒径分析。采用透析袋扩散法测定GK从GK-OCMC Nps中的释放情况。采用3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2-H-四氮唑溴盐法测定GK和GK-OCMC Nps对PC3细胞活力的影响。基于Cy5.5标记探针的荧光技术用于探究GK-OCMC Nps的细胞摄取情况。

结果

GK-OCMC NPs具有合适的粒径和zeta电位；呈球形，分散性良好。GK-OCMC NPs的药物释放具有pH依赖性。此外，细胞毒性研究和细胞摄取试验表明，GK-OCMC Nps显著增强了GK对PC3细胞的细胞毒性和细胞摄取。GK-OCMC Nps还显著促进了caspase-3和caspase-9的活性。

结论

GK-OCMC Nps是递送疏水性药物的潜在纳米载体，可提高水溶性和通透性，增强GK的抗增殖作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/1fa24f60ee0e/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/5c28609e0964/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/e2b6f81c6747/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/c9b02c4b8eaf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/1188426da121/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/ac65cb4644e9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/d38ce6798c1a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/1fa24f60ee0e/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/5c28609e0964/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/e2b6f81c6747/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/c9b02c4b8eaf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/1188426da121/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/ac65cb4644e9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/d38ce6798c1a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df43/8020349/1fa24f60ee0e/gr7.jpg

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