• Home
  • Search Results
  • pH-sensitive nanoformulated triptolide as a targeted therapeutic strategy for hepatocellular carcinoma.

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

ACS nano (2014-08-06)
Daishun Ling, Hongping Xia, Wooram Park, Michael J Hackett, Changyeong Song, Kun Na, Kam Man Hui, Taeghwan Hyeon
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
N,N-Dimethylformamide, anhydrous, 99.8%
Sigma-Aldrich
Tetrahydrofuran, anhydrous, ≥99.9%, inhibitor-free
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Dimethyl sulfoxide-d6, 99.9 atom % D
Sigma-Aldrich
Tetrahydrofuran, anhydrous, contains 250 ppm BHT as inhibitor, ≥99.9%
Sigma-Aldrich
Tetrahydrofuran, inhibitor-free, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Sigma-Aldrich
Dichloromethane, suitable for HPLC, ≥99.8%, contains amylene as stabilizer
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%
Sigma-Aldrich
N,N-Dimethylformamide, suitable for HPLC, ≥99.9%
Sigma-Aldrich
N,N-Dimethylformamide, ACS reagent, ≥99.8%
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Dimethyl sulfoxide-d6, 99.9 atom % D, contains 0.03 % (v/v) TMS
Sigma-Aldrich
Tetrahydrofuran, contains 250 ppm BHT as inhibitor, ACS reagent, ≥99.0%
Sigma-Aldrich
DCC, 99%
Sigma-Aldrich
4-(Dimethylamino)pyridine, ReagentPlus®, ≥99%
Sigma-Aldrich
Dichloromethane, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains 50-150 ppm amylene as stabilizer
Sigma-Aldrich
N,N-Dimethylformamide, for molecular biology, ≥99%
Sigma-Aldrich
Dichloromethane, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)
Sigma-Aldrich
Tetrahydrofuran, contains 250 ppm BHT as inhibitor, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide-d6, "100%", 99.96 atom % D
Sigma-Aldrich
Dimethyl sulfoxide-d6, 99.5 atom % D
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Triphosgene, reagent grade, 98%