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Updated: Sep 20, 2025
Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
A nucleus-targeting peptide antagonist towards EZH2 displays therapeutic efficacy for lung cancer
Mei Jiang1, Xiaocui Fang2, Lilusi Ma2
1CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China; Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, PR China.
Abstract:
EZH2 is an overexpressed nuclear protein associated with relatively poor survival and chemoresistance in lung cancer. In this study, a nucleus-targeting peptide antagonist EIP103 capable of penetrating cell membrane and nuclear envelope was identified, and has high binding affinity towards EZH2 localized in the nucleus of lung cancer cells. To improve the stability and therapeutic efficacy of EIP103, PEG-PE micelle encapsulated EIP103 (M-EIP103) was successfully conducted. In vitro results indicated that M-EIP103 exhibited better stability, higher intracellular uptake and stronger cytotoxicity than free EIP103 in H446 and A549 cells. Mechanistic studies suggested that M-EIP103 inhibited proliferation by down-regulating the H3K27me3 expression level in cancer cells. In vivo assays further confirmed that both EIP103 and M-EIP103 significantly inhibited lung cancer progression. Notably, enhanced therapeutic efficacy of EIP103 by PEG-PE micelle encapsulation could be identified. The observed anti-tumor activity of EIP103 and M-EIP103 demonstrated a promising therapy to improve clinical treatment of lung cancers as well as other EZH2-overexpressing malignant cancers. This study also illustrates the feasibility of developing targeted delivery of therapeutic peptides to nucleus for cancer therapy.
Insights
A novel peptide EIP103 targets the overexpressed EZH2 protein in lung cancer. Encapsulating EIP103 in PEG-PE micelles (M-EIP103) enhanced its stability and anti-tumor efficacy, showing promise for cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Drug Delivery
Background:
- Enhancer of Zeste Homolog 2 (EZH2) is overexpressed in lung cancer, correlating with poor survival and chemoresistance.
- Targeting EZH2 presents a therapeutic strategy for lung cancer and other malignancies.
Purpose of the Study:
- To identify and characterize a nucleus-targeting peptide antagonist (EIP103) for EZH2.
- To enhance the stability and therapeutic efficacy of EIP103 through PEG-PE micelle encapsulation (M-EIP103).
- To evaluate the in vitro and in vivo anti-tumor activity of EIP103 and M-EIP103.
Main Methods:
- Identification of nucleus-targeting peptide EIP103 with high binding affinity to nuclear EZH2.
- Formulation of PEG-PE micelle encapsulated EIP103 (M-EIP103).
- In vitro assays using H446 and A549 lung cancer cells to assess stability, uptake, cytotoxicity, and H3K27me3 levels.
- In vivo studies to evaluate tumor inhibition in lung cancer models.
Main Results:
- M-EIP103 demonstrated improved stability, cellular uptake, and cytotoxicity compared to free EIP103 in vitro.
- M-EIP103 effectively inhibited lung cancer cell proliferation by down-regulating H3K27me3 expression.
- Both EIP103 and M-EIP103 significantly inhibited lung cancer progression in vivo, with M-EIP103 showing enhanced efficacy.
Conclusions:
- PEG-PE micelle encapsulation significantly enhances the therapeutic efficacy of the EZH2 antagonist EIP103.
- EIP103 and M-EIP103 exhibit promising anti-tumor activity against lung cancer.
- This study validates the potential of targeted nuclear delivery of therapeutic peptides for cancer treatment.
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