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Published on: August 23, 2024
Intracellular Delivery of Stabilized Peptide Blocking MTDH-SND1 Interaction for Breast Cancer Suppression
Hailing Chen1, Meimiao Zhan1, Yaping Zhang2
1State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Abstract:
Triple-negative breast cancer is one of the most prevalent malignant cancers worldwide. Disrupting the MTDH-SND1 protein-protein interaction has recently been shown to be a promising strategy for breast cancer therapy. In this work, a novel potent stabilized peptide with a stronger binding affinity was obtained through rational structure-based optimization. Furthermore, a sulfonium-based peptide delivery system was established to improve the cell penetration and antitumor effects of stabilized peptides in metastatic breast cancer. Our study further broadens the in vivo applications of the stabilized peptides for blocking MTDH-SND1 interaction and provides promising opportunities for breast cancer therapy.
Insights
Researchers developed a stabilized peptide to disrupt the MTDH-SND1 interaction, a key target in triple-negative breast cancer. A novel delivery system enhances its effectiveness against metastatic breast cancer.
Area of Science:
- Oncology
- Biochemistry
- Drug Delivery
Background:
- Triple-negative breast cancer (TNBC) is a prevalent and aggressive malignancy.
- Targeting the MTDH-SND1 protein-protein interaction is a promising therapeutic strategy for TNBC.
- Developing effective delivery systems is crucial for peptide-based cancer therapies.
Purpose of the Study:
- To design and optimize a stabilized peptide targeting the MTDH-SND1 interaction.
- To develop a sulfonium-based delivery system for enhanced peptide efficacy in metastatic breast cancer.
- To evaluate the in vivo application and therapeutic potential of the optimized peptide delivery system.
Main Methods:
- Rational structure-based optimization was employed to create a potent stabilized peptide.
- A novel sulfonium-based peptide delivery system was synthesized and characterized.
- In vitro and in vivo studies were conducted to assess cell penetration and antitumor effects.
Main Results:
- A novel stabilized peptide with enhanced binding affinity for MTDH-SND1 was successfully developed.
- The sulfonium-based delivery system significantly improved peptide cell penetration and antitumor activity.
- The peptide delivery system demonstrated promising efficacy in preclinical models of metastatic breast cancer.
Conclusions:
- The developed stabilized peptide and its delivery system represent a promising therapeutic approach for triple-negative breast cancer.
- Blocking the MTDH-SND1 interaction via this novel peptide system offers new opportunities for TNBC treatment.
- Further in vivo studies support the potential of this strategy for clinical translation.
