Glioblastoma is a rapidly lethal cancer with a stringent need for new treatment strategies. In this study, we tested if chitosan-capped gold nanoparticles (Chit-GNPs) may overcome the limitations of drug concentrations by an increased cell internalisation in glioblastoma stem-like cells (GSCs) and if such GNPs could enhance the response to irradiation.
GSCs lines were isolated from glioblastoma tumor fragments and characterised with stemness and neural markers. Chitosan biopolymer was used as reducing and stabilizing agent to generate Chit-GNPs through an environmentally friendly synthesis procedure. The fabricated Chit-GNPs were characterized by UV-vis-NIR extinction spectroscopy, transmission electron microscopy and zeta potential measurements. GSCs and two normal cell lines were selected for in vitro investigations. The uptake and cytotoxicity of Chit-GNPs were evaluated relatively to that of citrate-capped gold nanospheres (GNPs) of similar size. Cell lines were treated with increasing concentrations of GNPs and Chit-GNPs and then irradiated with hypofractionated radiotherapy (3 consecutive fractions of 1, 2 Gy) and brachytherapy (one single fraction of 1 and 2 Gy). The effect was evaluated through the MTT cell viability test and confirmed with Trypan blue-based counting.
GSCs proved to express stem-cell markers and were highly resistant to radiotherapy. Their cell viability and proliferation were impaired by chit-GNPs with an IC50 of 10ug/mL, while remaining unaffected by simple GNP used in similar concentrations. Chit-GNPs were 15 nm in size, with a positive zeta potential and proved a superior cell internalisation compared to simple GNPs. Normal cell lines remained unaffected by GNPs and Chit-GNPs. Radiotherapy at the tested doses failed to give an additional anti-cancer effect when combined with GNP treatment.
The enhanced internalisation within GSCs and the cytotoxic effect of Chit-GNPs make this compound a suitable backbone for drug delivery in glioblastoma treatment, particularly as it proved a selective toxicity for cancer cells. Surprisingly, Chit-GNPs were highly cytotoxic to glioma cell lines irrespective of irradiation.
Clinical trial identification
Legal entity responsible for the study
Iuliu Hatieganu University of Medicine and Pharmacy
UEFISCDI - PNII-RU-TE-2014-4-0225 (ENERGY)
All authors have declared no conflicts of interest.