DNAzyme-Based nanoflowers for reversing P-glycoprotein-mediated multidrug resistance in breast cancer

基于脱氧核糖核酸酶的纳米花可逆转乳腺癌中 P 糖蛋白介导的多药耐药性

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作者:Linna Liang, Wendi Huo, Bei Wang, Lingzhi Cao, Haoran Huo, Yixin Liu, Yi Jin, Xinjian Yang

Abstract

Multidrug resistance (MDR) of tumors has been recognized as an important cause of chemotherapy failure, which is responsible for about 90% of cancer deaths. Therefore, it is desirable to develop a highly effective strategy to reverse tumor MDR for rebuilding the sensitivity of tumor cells towards chemodrugs. Here, self-assembled DNAzyme nanoflowers (NFs) constructed by rolling circle amplification (RCA) strategy were applied in doxorubicin (Dox) delivery for efficiently ablating Dox-resistant breast cancer. The encoded multiple DNAzymes could catalytically cleave P-glycoprotein (P-gp) mRNA which assists the efflux of chemodrugs, for reversing the MDR. The in vitro and in vivo results showed that the P-gp DNAzymes NFs not only had a high drug-loading capacity (69.21%) and acid-triggered biodegrade ability, but also effectively suppressed the expression of P-gp for reversing MDR of the tumor. Therefore, the DNAzyme-based drug delivery nanoplatform would be a promisingstrategyfor reversing MDR in cancer therapy.

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