Targeted core-shell nanoparticles for precise CTCF gene insert in treatment of metastatic breast cancer

Jialun Duan; Chunjie Bao; Ying Xie; Haitao Guo; Yixuan Liu; Jianwei Li; Rui Liu; Peishan Li; Jing Bai; Yan Yan; Limin Mu; Xueqi Li; Guiling Wang; Wanliang Lu

Bioactive Materials (May 2022)

Targeted core-shell nanoparticles for precise CTCF gene insert in treatment of metastatic breast cancer

Jialun Duan,
Chunjie Bao,
Ying Xie,
Haitao Guo,
Yixuan Liu,
Jianwei Li,
Rui Liu,
Peishan Li,
Jing Bai,
Yan Yan,
Limin Mu,
Xueqi Li,
Guiling Wang,
Wanliang Lu

Affiliations

Jialun Duan: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Chunjie Bao: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Ying Xie: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Haitao Guo: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Yixuan Liu: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Jianwei Li: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100875, China
Rui Liu: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Peishan Li: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Jing Bai: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Yan Yan: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Limin Mu: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Xueqi Li: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Guiling Wang: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Wanliang Lu: State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, And School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Corresponding author. School of Pharmaceutical Sciences Peking University Beijing 100191, China.

Journal volume & issue: Vol. 11
pp. 1 – 14

Abstract

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Clustered regularly interspaced short palindromic repeats (CRISPR) technology emerges a remarkable potential for cure of refractory cancer like metastatic breast cancer. However, how to efficiently deliver the CRISPR system with non-viral carrier remains a major issue to be solved. Here, we report a kind of targeted core-shell nanoparticles (NPs) carrying dual plasmids (pHR-pCas9) for precise CCCTC-binding factor (CTCF) gene insert to circumvent metastatic breast cancer. The targeted core-shell NPs carrying pHR-pCas9 can accomplish γGTP-mediated cellular uptake and endosomal escape, facilitate the precise insert and stable expression of CTCF gene, inhibit the migration, metastasis, and colonization of metastatic breast cancer cells. Besides, the finding further reveals that the inhibitory mechanism of metastasis could be associated with up-regulating CTCF protein, followed by down-regulating stomatin (STOM) protein. The study offers a universal nanostrategy enabling the robust non-viral delivery of gene-editing system for treatment of severe illness.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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