A nucleus-targeting peptide antagonist towards EZH2 displays therapeutic efficacy for lung cancer.

A549 Cells Cell Line, Tumor Cell Proliferation Enhancer of Zeste Homolog 2 Protein / metabolism Humans Lung Neoplasms / pathology Micelles Peptides
Antagonistic peptide Cancer therapy Nanomicelle Nucleus-targeting

Journal

International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127

Informations de publication

Date de publication:
25 Jun 2022
Historique:
received: 02 03 2022
revised: 18 05 2022
accepted: 02 06 2022
pubmed: 10 6 2022
medline: 22 6 2022
entrez: 9 6 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ijpharm.2022.121894 PMID: 35680109
pubmed: 35680109
pii: S0378-5173(22)00449-5
doi: 10.1016/j.ijpharm.2022.121894
pii:
doi:

Substances chimiques

Micelles 0
Peptides 0
EZH2 protein, human EC 2.1.1.43
Enhancer of Zeste Homolog 2 Protein EC 2.1.1.43

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

121894

Informations de copyright

Copyright © 2022 Elsevier B.V. All rights reserved.

Auteurs

Mei Jiang (M)

CAS 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.

Xiaocui Fang (X)

CAS 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.

Lilusi Ma (L)

CAS 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.

Mingpeng Liu (M)

CAS 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.

Mengting Chen (M)

CAS 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.

Jingyi Liu (J)

CAS 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.

Yanlian Yang (Y)

CAS 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. Electronic address: yangyl@nanoctr.cn.

Chen Wang (C)

CAS 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. Electronic address: wangch@nanoctr.cn.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules A549 › A nucleus-targeting peptide antagonist towards...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › A nucleus-targeting peptide antagonist towards...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › A nucleus-targeting peptide antagonist towards...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Protéines du groupe Polycomb › Complexe répresseur Polycomb-2 › Protéine-2 homologue de l'activateur de Zeste › A nucleus-targeting peptide antagonist towards...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A nucleus-targeting peptide antagonist towards...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › A nucleus-targeting peptide antagonist towards...
questionsmedicales.fr › Préparations pharmaceutiques › Micelles › A nucleus-targeting peptide antagonist towards...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › A nucleus-targeting peptide antagonist towards...