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Multimodal Nanoplatform with ROS Amplification to Overcome Multidrug Resistance in Prostate Cancer via Targeting
Yupeng Guan1,2, Hanqi Lei1, Chengyuan Xing2
1Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, P. R. China.
Abstract:
Chemotherapy remains the most essential treatment for prostate cancer, but multidrug resistance (MDR) contributes to chemotherapy failure and tumor-related deaths. The overexpression of P-glycoprotein (P-gp) is one of the main mechanisms behind MDR. Here, this work reports a multimodal nanoplatform with a reactive oxygen species (ROS) cascade for gas therapy/ferroptosis/chemotherapy in reversing MDR. The nanoplatform disassembles when responding to intracellular ROS and exerts three main functions: First, nitric oxide (NO) targeted delivery can reverse MDR by downregulating P-gp expression and inhibiting mitochondrial function. Second, ferrocene-induced ferroptosis breaks the redox balance in the tumor intracellular microenvironment and synergistically acts against the tumor. Third, the release of paclitaxel (PTX) is precisely controlled in situ in the tumor for chemotherapy that avoids damage to normal tissues. Excitingly, this multimodal nanoplatform is a promising weapon for reversing MDR and may provide a pioneering paradigm for synergetic cancer therapy.
Insights
This study introduces a novel nanoplatform that combats chemotherapy resistance in prostate cancer. It utilizes a reactive oxygen species (ROS) cascade for combined gas therapy, ferroptosis, and chemotherapy to overcome multidrug resistance (MDR).
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Multidrug resistance (MDR) is a major cause of chemotherapy failure in prostate cancer.
- P-glycoprotein (P-gp) overexpression is a key mechanism driving MDR.
- Novel therapeutic strategies are needed to overcome MDR and improve treatment outcomes.
Purpose of the Study:
- To develop a multimodal nanoplatform for synergistic cancer therapy.
- To investigate the potential of a reactive oxygen species (ROS) cascade for reversing MDR.
- To combine gas therapy, ferroptosis, and chemotherapy for enhanced prostate cancer treatment.
Main Methods:
- Design and synthesis of a ROS-responsive nanoplatform.
- Incorporation of nitric oxide (NO) for MDR reversal and mitochondrial function inhibition.
- Utilizing ferrocene to induce ferroptosis and disrupt tumor redox balance.
- Controlled release of paclitaxel (PTX) for targeted chemotherapy.
Main Results:
- The nanoplatform effectively disassembles in response to intracellular ROS.
- Nitric oxide (NO) delivery downregulated P-gp expression, reversing MDR.
- Ferrocene-induced ferroptosis synergistically targeted tumor cells.
- Precisely controlled paclitaxel (PTX) release achieved effective chemotherapy with reduced damage to normal tissues.
Conclusions:
- The developed multimodal nanoplatform shows promise in reversing MDR in prostate cancer.
- This approach offers a pioneering paradigm for synergistic cancer therapy.
- The nanoplatform demonstrates potential for overcoming chemotherapy resistance and improving patient outcomes.
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