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Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma
- Source :
- Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-16 (2021), Journal of Nanobiotechnology
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
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
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 14773155
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Nanobiotechnology
- Accession number :
- edsair.doi.dedup.....dc0264e3837109b31cb7967ffc0dacf5