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

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

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

Afiliación

Tu Q; 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, Kaife
Xia F; 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.
Meng Y; 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.
Wang C; 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.
Zhang H; 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.
Yao H; 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.
Fu Y; 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.
Guo P; 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 W; 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.
Zhou X; 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.
Zhou L; 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.
Gan L; 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.
Wang J; 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, Kaife
Han G; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China. Electronic address: hang@henu.edu.cn.
Qiu C; 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. Electronic address: cqiu@icmm.ac.cn.

Biomed Pharmacother ; 179: 117413, 2024 Sep 10.

Article en En | MEDLINE | ID: mdl-39260325

ABSTRACT

ABSTRACT

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.

Palabras clave

Brain Glioma; Delivery; Endoplasmic reticulum membrane; Nanoplexes; SiRNA

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