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Published on: April 27, 2018
ROS-responsive polyprodrug micelles carrying suicide genes in combination with chemotherapy and gene therapy for
Kai Li1, Sinan Tian1, Ke Sun1
1Department of Urology, Binzhou Medical University Hospital Binzhou Shandong 256500 P. R. China Dr_nwj327@bzmc.edu.cn.
Abstract:
Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.
Insights
This study developed novel cationic micelles for prostate cancer treatment. These nanocarriers deliver both chemotherapy and gene therapy, targeting cancer cells while minimizing side effects.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Prostate cancer incidence rises with age, necessitating effective treatments.
- Chemotherapy is a primary strategy but causes significant side effects.
- Nanocarriers offer improved drug delivery and targeting, with cationic types enabling gene therapy.
Purpose of the Study:
- To develop a polyprodrug-based cationic micelle for simultaneous delivery of chemotherapeutics and nucleic acids.
- To create a targeted delivery system for prostate cancer, reducing off-target toxicity.
- To investigate the combined therapeutic effect of chemotherapy and gene therapy in prostate cancer models.
Main Methods:
- Synthesized amphiphilic block polymers by linking hydroxycamptothecin (HCPT) to polyethyleneimine (PEI) via ROS-responsive linkers.
- Formed cationic micelles capable of co-delivering HCPT and suicide genes.
- Evaluated the drug release mechanism triggered by reactive oxygen species (ROS) in tumor cells.
Main Results:
- The cationic micelles successfully co-delivered hydroxycamptothecin (HCPT) and suicide genes.
- ROS-responsive micelles released their payload specifically in high-ROS tumor environments.
- Demonstrated an ideal therapeutic effect in prostate cancer cells through combined chemotherapy and gene therapy.
Conclusions:
- Developed a novel polyprodrug-based cationic micelle for dual drug and gene delivery.
- The ROS-triggered release system effectively targets prostate cancer cells, enhancing efficacy and reducing side effects.
- Co-delivery of chemotherapy and suicide gene therapy shows significant therapeutic potential for prostate cancer.
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