AI Article Synopsis
- - The epidermal growth factor receptor (EGFR) is crucial in tumor development and is a key target for treating malignant gliomas, but using small interfering RNA (siRNA) to degrade EGFR mRNA faces challenges like poor targeting and degradation in lysosomes.
- - The research presents a novel siEGFR nanoplex (PEhCv/siEGFR NPs) that combines polyethylene glycol (PEG) and endoplasmic reticulum membrane coatings to improve targeting and uptake in brain gliomas.
- - These nanoplexes showed significantly better siEGFR gene silencing in lab and animal models, potentially leading to more effective nucleic acid-based cancer therapies in the future.
Article 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.
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| http://dx.doi.org/10.1016/j.biopha.2024.117413 | DOI Listing |
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