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In Vitro Biochemical Assays using Biotin Labels to Study Protein-Nucleic Acid Interactions
Published on: July 17, 2019
A biotin guided PtIV amphiphilic prodrug synergized with CDK4/6 inhibition for enhanced tumor targeted therapy
Shaoming Zhu1, Jiaxu Li2,3, Hao Sun4
1Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. wangww627@163.com.
Abstract:
Platinum-based chemotherapy has been the first-line treatment for advanced bladder cancer for decades, but its durability and safety remain important challenges. Targeted delivery and other precision medicine bring hope to fight cancer. In this study, we present a novel targeted therapy utilizing a biotin receptor-targeting lipid PtIV prodrug amphiphile, which encapsulates a CDK4/6 inhibitor into BPtIV@Rib. CDK4/6 inhibitors have the potential to combat breast cancer and enhance sensitivity to cisplatin, thereby improving its therapeutic efficacy. Our findings demonstrate that BPtIV@Rib also exhibits excellent bladder tumor-targeting capability, resulting in increased accumulation of Pt and ribociclib (Rib) at the tumor site. The combination of PtIV and Rib leads to substantial tumor growth suppression while minimizing synergistic toxicity compared to conventional therapies. In conclusion, this combination therapy represents a promising strategy for enhanced targeted treatment of bladder cancer, potentially improving patient outcomes while reducing adverse effects.
Insights
This study introduces a novel targeted therapy for advanced bladder cancer, combining platinum (Pt) and a CDK4/6 inhibitor (Rib) for enhanced tumor suppression and reduced toxicity.
Area of Science:
- Oncology
- Nanomedicine
- Drug Delivery
Background:
- Platinum-based chemotherapy is a standard first-line treatment for advanced bladder cancer.
- Challenges with current treatments include limited durability and significant safety concerns.
- Targeted delivery and precision medicine offer potential improvements in cancer therapy.
Purpose of the Study:
- To develop and evaluate a novel targeted therapy for bladder cancer.
- To investigate the efficacy of a biotin receptor-targeting lipid Pt(IV) prodrug amphiphile encapsulating a CDK4/6 inhibitor (ribociclib).
- To assess the combination therapy's tumor-targeting capability, therapeutic efficacy, and safety profile.
Main Methods:
- Synthesis of a novel lipid-based nanoparticle system (BPtIV@Rib) encapsulating a platinum(IV) prodrug and ribociclib.
- Evaluation of the system's ability to target bladder tumors via biotin receptor-mediated uptake.
- Assessment of platinum and ribociclib accumulation in tumor tissues.
- In vivo studies to evaluate tumor growth suppression and toxicity compared to conventional treatments.
Main Results:
- BPtIV@Rib demonstrated excellent bladder tumor-targeting capability.
- Increased accumulation of platinum and ribociclib was observed at the tumor site.
- The combination therapy significantly suppressed tumor growth.
- Synergistic toxicity was minimized compared to conventional therapies.
Conclusions:
- The developed BPtIV@Rib represents a promising targeted combination therapy for advanced bladder cancer.
- This strategy enhances therapeutic efficacy by increasing drug accumulation at the tumor site.
- The approach holds potential for improving patient outcomes while reducing adverse effects.
