The siEGFR nanoplexes for the enhanced brain glioma treatment: Endoplasmic reticulum biomimetic strategy to induce homing effect and non-degradable intracellular transport

Qingchao Tu; Fei Xia; Yuqing Meng; Chen Wang; Hao Zhang; Hailu Yao; Yuanfeng Fu; Pengbo Guo; Weiqi Chen; Xinyu Zhou; Li Zhou; Licheng Gan; Jigang Wang; Guang Han; Chong Qiu

Biomedicine & Pharmacotherapy (Oct 2024)

The siEGFR nanoplexes for the enhanced brain glioma treatment: Endoplasmic reticulum biomimetic strategy to induce homing effect and non-degradable intracellular transport

Qingchao Tu,
Fei Xia,
Yuqing Meng,
Chen Wang,
Hao Zhang,
Hailu Yao,
Yuanfeng Fu,
Pengbo Guo,
Weiqi Chen,
Xinyu Zhou,
Li Zhou,
Licheng Gan,
Jigang Wang,
Guang Han,
Chong Qiu

Affiliations

Qingchao Tu: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China
Fei Xia: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Yuqing Meng: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Chen Wang: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Hao Zhang: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Hailu Yao: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Yuanfeng Fu: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Pengbo Guo: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Weiqi Chen: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Xinyu Zhou: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Li Zhou: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Licheng Gan: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Jigang Wang: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China; Department of Nephrology,Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen ClinicalResearch Center for Geriatric, Shenzhen People's Hospital (The Second ClinicalMedical College, Jinan University, The First Affiliated Hospital, SouthernUniversity of Science and Technology), Shenzhen 518020, China; Corresponding author at: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Guang Han: State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China; Corresponding authors.
Chong Qiu: State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Corresponding authors.

Journal volume & issue: Vol. 179
p. 117413

Abstract

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The epidermal growth factor receptor (EGFR) plays a pivotal role in tumor progression and is an essential therapeutic target for treating malignant gliomas. Small interfering RNA (siRNA) has the potential to selectively degrade EGFR mRNA, yet its clinical utilization is impeded by various challenges, such as inefficient targeting and limited escape from lysosomes. Our research introduces polyethylene glycol (PEG) and endoplasmic reticulum membrane-coated siEGFR nanoplexes (PEhCv/siEGFR NPs) as an innovative approach to brain glioma therapy by overcoming several obstacles: 1) Tumor-derived endoplasmic reticulum membrane modifications provide a homing effect, facilitating targeted accumulation and cellular uptake; 2) Endoplasmic reticulum membrane proteins mediate a non-degradable ''endosome-Golgi-endoplasmic reticulum'' transport pathway, circumventing lysosomal degradation. These nanoplexes demonstrated significantly enhanced siEGFR gene silencing in both in vitro and in vivo U87 glioma models. The findings of this study pave the way for the advanced design and effective application of nucleic acid-based therapeutic nanocarriers.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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