Glioblastomas are difficult to treat due to the blood-brain barrier and drug resistance. To improve the efficacy of treating glioblastomas with selenium nanoparticles (Se-NPs), Se-NPs were coated with chitosan in the presented study.
INHIBITING METASTASIS AND IMPROVING CHEMOSENSITIVITY VIA CHITOSAN-COATED SELENIUM NANOPARTICLES FOR BRAIN CANCER THERAPY
Dana, P.; Pimpha, N.; Chaipuang, A.; Thumrongsiri, N.; Tanyapanyachon, P.; Taweechaipaisankul, A.; Chonniyom, W.; Watcharadulyarat, N.; Sathornsumetee, S.; Saengkrit, N. Inhibiting metastasis and improving chemosensitivity via chitosan-coated selenium nanoparticles for brain cancer therapy. Nanomaterials 2022, 12, 2606. https://doi.org/10.3390/nano12152606
Glioblastoma is the most common and aggressive type of malignant brain tumor in adults. Besides a poor quality of life, the chances of survival are low. This is due to problems in treatment, on the one hand drug resistance occurs, on the other hand only about 1 % of the drug reaches its destination due to the blood-brain barrier. For this reason, new strategies are urgently needed to enable more efficient treatment.
Selenium (Se) is an essential element needed by the body to maintain its functions. Due to its pro-oxidant properties, Se is used as an adjuvant in chemo- and radiotherapy of e.g. liver, breast or brain cancer. However, Se is toxic in high doses and its uptake is difficult to regulate.
To reduce toxicity and improve biocompatibility, Se can be bound to nanoparticles (NPs). In vivo and in vitro, SeNPs have already been shown to have good efficiency and tolerable toxicity. To further improve the stability and therapeutic effect of SeNPs, the surface of these can be optimized with polymers such as chitosan.
In the presented study, the inhibitory effect of chitosan-coated SeNPs on the aggressiveness of GBM cells in terms of cell proliferation, migration and invasion is investigated in a 3D spheroid tumor model.
- CS-SeNPs showed significantly reduced particle diameter at 88.66 ± 0.65 nm, 88.90 ± 0.57 nm, and 91.45 ± 2.57 nm compared to Se-NPs (417.60 ± 46.17 nm)
- Reduced PDI between 0.2±0.01 and 0.23±0.02 (SeNPs: 0.48 ± 0.08) indicates improved particle stability
- Stable particle size and zeta potential of more than 30 mV over 15 days.
- 2% CS-SeNPs showed great selectivity between U87 cells (glioblastoma cells) and fibroblasts (healthy cells) with the lowest cell viability of U87 cells and at the same time the lowest cytotoxicity to fibroblasts
- Improvement of the sensitivity of U87 cells to the chemotherapeutic agent 5-fluorouracil by 0.2% CS-SeNPs
- Inhibition of cell migration and cell invasion of glioblastoma cells by inhibition of MMP-2/9 activities
- Enhancement of cellular uptake of CS-SeNPs in U87 cells by chitosan coating.
- In vitro evidence that CS-SeNPs are potentially able to cross the blood-brain barrier
Summary: In the presented study, CS-SeNPs were successfully synthesized, which exhibited improved stability and smaller size compared to SeNPs. Moreover, 0.2% CS-SeNPs in particular showed improved antitumor activity against glioblastoma cells with only minor effects on fibroblasts. In an in vitro model, possible transport across the blood-brain barrier was demonstrated, which is essential for more efficient treatment of glioblastoma. To further assess the potential of CS-SeNPs further experiments in vivo have to be performed.