Journal
MOLECULAR PHARMACEUTICS
Volume 17, Issue 4, Pages 1415-1427Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c00138
Keywords
multidrug resistance; doxorubicin; quercetin; mixed micelles; combination strategy; reversal mechanism
Funding
- National Natural Science Foundation of China [81873198]
- Program of Shanghai Academic/Technology Research Leader [19XD1423700]
- Shanghai Natural Science Foundation [18ZR1436400, 19ZR1444200]
Ask authors/readers for more resources
The therapeutic efficacy of chemotherapy in many types of hematological malignancies and solid tumors is dramatically hindered by multidrug resistance (MDR). This work presents a combination strategy of pretreatment of MDA-MB-231/MDR1 cells with quercetin (QU) followed by doxorubicin (DOX) to overcome MDR, which can be delivered by mixed micelles composed of the reduction-sensitive hyaluronic acid-based conjugate and D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate. The combination strategy can enhance the cytotoxicity of DOX on MDA-MB-231/MDR1 cells by increasing intracellular DOX accumulation and facilitating DOX-induced apoptosis. The probable MDR reversal mechanisms are that the pretreatment cells with QU-loaded mixed micelles downregulate P-glycoprotein expression to decrease DOX efflux as well as initiate mitochondria-dependent apoptotic pathways to accelerate DOX-induced apoptosis. In addition, this combination strategy can not only potentiate in vivo tumor-targeting efficiency but also enhance the antitumor effect in MDA-MB-231/MDR1-bearing nude mice without toxicity or side effects. This research suggests that the co-administration of natural compounds and chemotherapeutic drugs could be an effective strategy to overcome tumor MDR, which deserves further exploration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available