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

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 promising strategy for reversing MDR in cancer therapy. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Tumor multidrug resistance is a major cause of chemotherapy failure, and reversing tumor multidrug resistance is crucial for increasing the sensitivity of tumor cells to chemodrugs. The self-assembled DNAzyme nanoflowers can efficiently reverse multidrug resistance, enhance drug loading capacity, and suppress P-glycoprotein expression.