Folate and Pegylated Aliphatic Polyester Nanoparticles for Targeted Anticancer Drug Delivery
| Autor: | Eftychia Angelou, Avgi Tsolou, Dimitrios N. Bikiaris, Maria Koffa, Stylianos Didaskalou, Konstantinos Avgoustakis, Bogos Agianian |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Biophysics
Pharmaceutical Science Bioengineering 02 engineering and technology 010402 general chemistry Endocytosis 01 natural sciences Biomaterials chemistry.chemical_compound Drug Discovery medicine Cytotoxicity Chemistry Pinocytosis Organic Chemistry technology industry and agriculture Cancer General Medicine 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Paclitaxel Folate receptor Drug delivery Cancer cell Cancer research 0210 nano-technology |
| Zdroj: | International Journal of Nanomedicine. 15:4899-4918 |
| ISSN: | 1178-2013 |
| Popis: | Purpose The use of chemotherapeutic agents to combat cancer is accompanied by high toxicity due to their inability to discriminate between cancer and normal cells. Therefore, cancer therapy research has focused on the targeted delivery of drugs to cancer cells. Here, we report an in vitro study of folate-poly(ethylene glycol)-poly(propylene succinate) nanoparticles (FA-PPSu-PEG-NPs) as a vehicle for targeted delivery of the anticancer drug paclitaxel in breast and cervical cancer cell lines. Methods Paclitaxel-loaded-FA-PPSu-PEG-NPs characterization was performed by in vitro drug release studies and cytotoxicity assays. The NPs cellular uptake and internalization mechanism were monitored by live-cell imaging in different cancer cell lines. Expression of folate receptor-α (FOLR1) was examined in these cell lines, and specific FOLR1-mediated entry of the FA-PPSu-PEG-NPs was investigated by free folic acid competition. Using inhibitors for other endocytic pathways, alternative, non-FOLR1 dependent routes for NPs uptake were also examined. Results Drug release experiments of Paclitaxel-loaded PPSu-PEG-NPs indicated a prolonged release of Paclitaxel over several days. Cytotoxicity of Paclitaxel-loaded PPSu-PEG-NPs was similar to free drug, as monitored in cancer cell lines. Live imaging of cells treated with either free Paclitaxel or Paclitaxel-loaded PPSu-PEG-NPs demonstrated tubulin-specific cell cycle arrest, with similar kinetics. Folate-conjugated NPs (FA-PPSu-PEG-NPs) targeted the FOLR1 receptor, as shown by free folic acid competition of the FA-PPSu-PEG-NPs cellular uptake in some of the cell lines tested. However, due to the differential expression of FOLR1 in the cancer cell lines, as well as the intrinsic differences between the different endocytic pathways utilized by different cell types, other mechanisms of nanoparticle cellular entry were also used, revealing that dynamin-dependent endocytosis and macropinocytosis pathways mediate, at least partially, cellular entry of the FA-PPSu-PEG NPs. Conclusion Our data provide evidence that Paclitaxel-loaded-FA-PPSu-PEG-NPs can be used for targeted delivery of the drug, FA-PPSu-PEG-NPs can be used as vehicles for other anticancer drugs and their cellular uptake is mediated through a combination of FOLR1 receptor-specific endocytosis, and macropinocytosis. The exploration of the different cellular uptake mechanisms could improve treatment efficacy or allow a decrease in dosage of anticancer drugs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|