1. Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
- Author
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Xiamei Guo, Li Zhang, Fei Xie, Cheng Shen, Chao Luo, Yali Jun, Keping Xu, Qilong Wang, Xiaojuan Yu, Zhengwei Zhang, Longfei Liu, Yong Gao, and Xiang Li
- Subjects
Esophageal Neoplasms ,medicine.medical_treatment ,Biomedical Engineering ,Mice, Nude ,Pharmaceutical Science ,Medicine (miscellaneous) ,Apoptosis ,Bioengineering ,Endocytosis ,Applied Microbiology and Biotechnology ,Target therapy ,Targeted therapy ,miR-375 ,Mice ,Mir-375 ,Esophageal squamous cell carcinoma ,Cell Line, Tumor ,RNA nanoparticles ,medicine ,Medical technology ,Animals ,Humans ,Molecular Targeted Therapy ,Epidermal growth factor receptor ,R855-855.5 ,biology ,Chemistry ,Research ,EGFR aptamer ,RNA ,Cancer ,Esophageal cancer ,medicine.disease ,ErbB Receptors ,MicroRNAs ,Cancer research ,biology.protein ,Nanoparticles ,Molecular Medicine ,Female ,Nanocarriers ,Nanoparticle Drug Delivery System ,Aptamers, Peptide ,TP248.13-248.65 ,Biotechnology - Abstract
Background Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. Results Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. Conclusion This strategy may provide a practical approach for targeted therapy of ESCC. Graphical Abstract
- Published
- 2021