Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 15, Issue 1, Pages 86-97Publisher
ELSEVIER
DOI: 10.1016/j.nano.2018.09.002
Keywords
Triptolide; Nanoparticle; Hepatocellular carcinoma; Network pharmacology; Toxicity
Funding
- National Natural Science Foundation of China [81673834]
- Beijing Nova Program [Z1511000003150126]
- Fundamental Research Funds for the Central Public Welfare Research Institutes [Z2017082, L2017018]
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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Current therapies present significant limitations. Triptolide (TP) is highly effective against multiple cancers including HCC. However, high toxicity, low water solubility, and unknown therapeutic targets limit its clinical application. Herein, we designed galactosylated-chitosan-TP-nanoparticles (GC-TP-NPs) with high drug loading capacities for targeted delivery to HCC. In addition to a sustained release pattern, an efficient asialoglycoprotein receptor mediated cellular uptake in vitro, and high liver tumor accumulation in vivo, GC-TP-NPs showed lower systemic and male reproductive toxicities than free TP. Importantly, GC-TP-NPs retained the anti-cancer activities of the free TP, exerting the same pro-apoptotic and anti-proliferative effects on HCC cells in vitro, and displayed higher efficacies in reducing tumor sizes in vivo. Further investigation revealed that GC-TP-NPs induced cancer cell apoptosis via blocking TNF/NF-kappa B/BCL2 signaling. Collectively, GC-TP-NP represents a promising candidate in halting liver cancer progression while minimizing systemic toxicity. (C) 2018 Elsevier Inc. All rights reserved.
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