Journal
ACTA PHARMACOLOGICA SINICA
Volume 38, Issue 6, Pages 943-953Publisher
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2017.45
Keywords
magnetic nanoparticle; transferrin receptors; paclitaxel; targeted drug delivery; MCF-7 breast cancer; U-87 glioma cells; nanomedicine
Funding
- National University of Singapore (NUS) [R279-000-357-275]
- National Medical Research Council (NMRC, Singapore) [NMRC/EDG11may084]
- National Natural Science Foundation of China [81402885]
- Chinese Scholarship Council
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Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D, L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solidin-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors.
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