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PH-sensitive nanoformulated triptolide as a targeted therapeutic strategy for hepatocellular carcinoma

Cited 73 time in webofscience Cited 77 time in scopus
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Title
PH-sensitive nanoformulated triptolide as a targeted therapeutic strategy for hepatocellular carcinoma
Author(s)
Daishun Ling; Xia H.; Park W.; Michael J. Hackett; Changyeong Song; Na K.; Hui K.M.; Taeg Hwan Hyeon
Subject
hepatocellular carcinoma . triptolide . pH sensitive polymer . targeted cancer therapy . drug delivery
Publication Date
2014-08
Journal
ACS NANO, v.8, no.8, pp.8027 - 8039
Publisher
AMER CHEMICAL SOC
Abstract
Hepatocellular carcinoma (HCC) has one of the worst prognoses for survival as it is poorly responsive to both conventional chemotherapy and mechanism-directed therapy. This results from a lack of therapeutic concentration in the tumor tissue coupled with the highly toxic off-site effects exhibited by these compounds. Consequently, we believe the best packaging for holistic therapy for HCC will involve three components: a potent therapeutic, a rationally designed drug delivery vehicle to enrich the target site concentration of the drug, and a surface ligand that can enable a greater propensity to internalization by tumor cells compared to the parenchyma. We screened a library containing hundreds of compounds against a panel of HCC cells and found the natural product, triptolide, to be more effective than sorafenib, doxorubicin, and daunorubicin, which are the current standards of therapy. However, the potential clinical application of triptolide is limited due to its poor solubility and high toxicity. Consequently, we synthesized tumor pH-sensitive nanoformulated triptolide coated with folate for use in an HCC-subpopulation that overexpresses the folate receptor. Our results show triptolide itself can prevent disease progression, but at the cost of significant toxicity. Conversely, our pH-sensitive nanoformulated triptolide facilitates uptake into the tumor, and specifically tumor cells, leading to a further increase in efficacy while mitigating systemic toxicity.
URI
https://pr.ibs.re.kr/handle/8788114/947
DOI
10.1021/nn502074x
ISSN
1936-0851
Appears in Collections:
Center for Nanoparticle Research(나노입자 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
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