Study and evaluation of nucleolin-targeted delivery of magnetic PLGA-PEG nanospheres loaded with doxorubicin to C6 glioma cells compared with low nucleolin-expressing L929 cells
Abstract
Magnetic nanoparticulate systems based on polymeric materials such as poly (lactic-co-glycolic acid) (PLGA 1) are being studied for their potential applications in targeted therapy and imaging of malignant tumors. In the current study, superparamagnetic iron oxide nanocrystals (SPIONs 2) and doxorubicin (Dox 3) were entrapped in the PLGA-based nanoparticles via a modified multiple emulsion solvent evaporation method. Furthermore, SPIO/Dox-NPs 4 were conjugated to anti-nucleolin AS1411 aptamer (Apt 5) and their targeting ability was investigated in high nucleolin-expressing C6 glioma cells compared to low nucleolin-expressing L929 cells. The NPs exhibited a narrow size distribution with mean diameter of ~170nm and an appropriate SPION content (~18% of total polymer weight) with a sufficient saturation magnetization value of 5.9emu/g which is suitable for imaging objectives. They manifested an increased Dox release at pH5.5 compared to pH7.4, with initial burst release (within 24h) followed by sustained release of Dox for 36days. The Apt conjugation to NPs enhanced cellular uptake of Dox in C6 glioma cells compared to L929 cells. Similarly, the Apt-NPs increased the cytotoxicity effect of Dox compared with NPs and Dox solution (f-Dox) alone. In conclusion, the Apt-NPs were found to be a promising delivery system for therapeutic and diagnostic purposes.
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AS1411 possesses a specific interaction with nucleolin, an important biomarker in various cancer cells that promotes tumor growth and metastasis.
“Recently, AS1411 was reported to possess a specific interaction with nucleolin, an important biomarker in various cancer cells to promote the tumor growth and metastasis.48,49”
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Aptamer-guided nanomedicines for anticancer drug delivery
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- Authors
- Mosafer, J., Teymouri, M., Abnous, K., Tafaghodi, M., & Ramezani, M.
- Affiliations
- Mashhad University of Medical Sciences (IR)
- Gonabad University of Medical Sciences (IR)
- Corresponding author
- Ramezani, Mohammad
- Venue
- Materials Science and Engineering: C
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 72
- Pages
- 123-133
- ISSN
- 0928-4931 (ISSN-L)
- OpenAlex
- W2553894721
- Cited by
- 60
- References
- 43
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 3 · 2019: 13 · 2018: 12 · 2017: 6
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Materials Science and Engineering C (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Keywords
- nucleolin, AS1411 aptamer, targeted drug delivery, PLGA-PEG nanoparticles, superparamagnetic iron oxide nanoparticles, doxorubicin, C6 glioma cells, L929 fibroblasts, pH-responsive drug release, cellular uptake, cytotoxicity
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Nucleolin, Animals, Antibiotics, Antineoplastic, Cell Survival, Dextrans, Doxorubicin, Drug Carriers, Glioma, Half-Life, Immunohistochemistry, Particle Size, Phosphoproteins, Polyethylene Glycols, Polyglycolic Acid, RNA-Binding Proteins, Lactic Acid, Cell Line, Tumor, Mice, Rats, Aptamers, Nucleotide, Nanospheres, Magnetite Nanoparticles, Drug Liberation
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