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Updated: Jul 16, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Multifunctional DNA nano-sponge system for targeted sensitization of ovarian cancer chemotherapy via metabolic
Dong Kejun1, Hu Hao1, Cheng Shuangshuang1
1Department of Obstetrics and Gynecology, Union Hospital and Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
The inefficacy of chemotherapy in ovarian cancer, hindered by poor targeting and multiple drug resistance, is intricately linked to the tumor micro-environment and abnormal metabolic patterns. Here, we present ZnOov@DS-DOX, an innovative nanomaterial that integrates small-sized ZnO nanoparticles with oxygen vacancies, embedded within 2D-ZnMOF and encapsulated in a DNA nanosponge, to enhance doxorubicin delivery. This system targets ovarian cancer cells specifically through the MUC1 aptamer and remodels metabolic signaling within the tumor microenvironment. ZnOov alleviates hypoxia and reduces chemoresistance by catalyzing H2O2, while Zn2+ release activates DNAzymes to target HIF-1a mRNA. The system reduces the efflux of chemotherapy drugs and inhibits cellular glycolysis. Disrupting the Warburg effect enhances mitochondrial respiration, increases ROS levels, disrupts the redox system, and induces ferroptosis, thereby significantly improving therapeutic efficacy. The uptake rate of ovarian cancer cells for the system was nearly 15 times higher than that of normal cells. Following treatment, the IC50 value of ovarian cancer cells decreased by approximately 72.7 %. Our in vitro and in vivo studies demonstrate that ZnOov@DS-DOX effectively modulates tumor metabolic pathways, mitigates drug resistance, and enhances treatment outcomes, representing a significant advancement in nanomedicine and cancer therapy.
Insights
This study introduces ZnOov@DS-DOX, a novel nanomedicine for ovarian cancer. It effectively targets cancer cells, overcomes drug resistance by modulating tumor metabolism, and significantly improves therapeutic outcomes.
Area of Science:
- Nanomedicine
- Biomaterials Science
- Oncology
Background:
- Chemotherapy inefficacy for ovarian cancer is linked to poor targeting, drug resistance, tumor microenvironment, and metabolic dysregulation.
- Developing targeted drug delivery systems that overcome resistance and modulate the tumor microenvironment is crucial for improving ovarian cancer treatment.
Purpose of the Study:
- To develop and evaluate ZnOov@DS-DOX, a novel nanomaterial for enhanced doxorubicin delivery in ovarian cancer.
- To investigate the system's ability to target ovarian cancer cells, remodel the tumor microenvironment, and overcome chemoresistance.
Main Methods:
- Fabrication of ZnOov@DS-DOX nanomaterial integrating ZnO nanoparticles with oxygen vacancies, 2D-ZnMOF, and DNA nanosponge.
- Incorporation of MUC1 aptamer for specific cancer cell targeting.
- Assessment of hypoxia alleviation, chemoresistance mitigation, metabolic pathway modulation (Warburg effect disruption), and ferroptosis induction in vitro and in vivo.
Main Results:
- ZnOov@DS-DOX demonstrated a nearly 15-fold higher uptake rate in ovarian cancer cells compared to normal cells.
- The system significantly reduced the IC50 value of ovarian cancer cells by approximately 72.7%.
- In vitro and in vivo studies confirmed effective modulation of tumor metabolic pathways, mitigation of drug resistance, and enhanced therapeutic efficacy.
Conclusions:
- ZnOov@DS-DOX represents a promising nanomedicine for ovarian cancer therapy.
- The system effectively targets cancer cells, alleviates tumor hypoxia, overcomes drug resistance, and disrupts the Warburg effect, leading to improved treatment outcomes.
- This approach offers a significant advancement in nanomedicine for enhancing cancer treatment efficacy.
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