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Updated: Oct 12, 2025
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
DNAzyme-Based nanoflowers for reversing P-glycoprotein-mediated multidrug resistance in breast cancer
Linna Liang1, Wendi Huo2, Bei Wang2
1College of Chemistry & Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, PR China.
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.
Insights
This study introduces DNAzyme nanoflowers for doxorubicin delivery, effectively reversing multidrug resistance in breast cancer by targeting P-glycoprotein mRNA. This approach enhances chemotherapy efficacy against resistant tumors.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapy
Background:
- Multidrug resistance (MDR) in tumors is a major cause of chemotherapy failure, leading to approximately 90% of cancer-related deaths.
- Reversing MDR is crucial for improving treatment outcomes and rebuilding tumor cell sensitivity to chemotherapeutic drugs.
Purpose of the Study:
- To develop a novel DNA nanoplatform for targeted drug delivery and overcoming multidrug resistance in doxorubicin-resistant breast cancer.
- To investigate the efficacy of self-assembled DNAzyme nanoflowers (NFs) in reversing MDR by targeting P-glycoprotein (P-gp).
Main Methods:
- Construction of DNAzyme nanoflowers (NFs) using rolling circle amplification (RCA) for doxorubicin (Dox) delivery.
- In vitro and in vivo evaluation of the NFs' drug-loading capacity, acid-triggered biodegradability, and ability to suppress P-gp expression.
Main Results:
- The DNAzyme NFs demonstrated a high drug-loading capacity of 69.21% and acid-triggered biodegradability.
- Effective suppression of P-glycoprotein (P-gp) expression was observed, indicating successful reversal of MDR.
- Significant ablation of doxorubicin-resistant breast cancer was achieved in both in vitro and in vivo models.
Conclusions:
- DNAzyme-based drug delivery nanoplatforms show significant promise for reversing multidrug resistance in cancer therapy.
- The developed P-gp DNAzymes NFs offer a viable strategy for enhancing the efficacy of existing chemotherapeutic agents against resistant cancers.
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