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

- Dox-containing PLGA-nanoparticle improves cancerous cytotoxicity of free Dox.
- Anti-nucleolin aptamer-nanoparticle leads to targeted cell delivery of drug.
- SPION containing PLGA-nanoparticle is apt for imaging purposes of tumors.
- PLGA releases doxorubicin inside cells, not outside the cells.
- PLGA could lead to improved drug retention in serum.

Magnetic nanoparticulate systems based on polymeric materials such as poly (lactic-co-glycolic acid) (PLGA1) are being studied for their potential applications in targeted therapy and imaging of malignant tumors. In the current study, superparamagnetic iron oxide nanocrystals (SPIONs2) and doxorubicin (Dox3) were entrapped in the PLGA-based nanoparticles via a modified multiple emulsion solvent evaporation method. Furthermore, SPIO/Dox-NPs4 were conjugated to anti-nucleolin AS1411 aptamer (Apt5) 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 ~ 170 nm and an appropriate SPION content (~ 18% of total polymer weight) with a sufficient saturation magnetization value of 5.9 emu/g which is suitable for imaging objectives. They manifested an increased Dox release at pH 5.5 compared to pH 7.4, with initial burst release (within 24 h) followed by sustained release of Dox for 36 days. 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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