Nanoparticle Conjugation of Ginsenoside Rg3 Inhibits Hepatocellular Carcinoma Development and Metastasis

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2020-01, Vol.16 (2), p.e1905233-n/a
• Main Authors: Ren, Zhigang, Chen, Xinmei, Hong, Liangjie, Zhao, Xiaoxiong, Cui, Guangying, Li, Ang, Liu, Yang, Zhou, Lina, Sun, Ranran, Shen, Shen, Li, Juan, Lou, Jiamin, Zhou, Heqi, Wang, Junmei, Xu, Guowang, Yu, Zujiang, Song, Yujun, Chen, Xinhua
• Format: Article
• Language: English
• Subjects: Animals; Cancer; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Conjugation; Fatty acids; ginsenoside Rg3; Ginsenosides - chemistry; Ginsenosides - pharmacology; gut microbiota; hepatocellular carcinoma; Humans; Iron oxides; Liver cancer; Liver Neoplasms - pathology; Medical prognosis; Metabolism; metabolomics; Metastasis; Mice; Microbiota; Microorganisms; Morphology; nanomedicine; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Neoplasm Metastasis; Therapy
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201905233

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe3O4 nanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamine‐induced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC‐induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty‐nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor‐dominant metabolomics. NpRg3 administration decreases 3‐indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy. An effective treatment for hepatocellular carcinoma (HCC) remains urgent. Fe@Fe3O4 nanoparticles are innovatively conjugated with ginsenoside Rg3 (NpRg3) and it is found that NpRg3 application significantly prolongs the survival of HCC mice. Nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.