Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells.
BACKGROUND
Neuroblastoma, a frequently occurring solid tumour in children, remains a therapeutic challenge as existing imaging tools are inadequate for proper and accurate diagnosis, resulting in treatment failures. Nanoparticles have recently been introduced to the field of cancer research and promise remarkable improvements in diagnostics, targeting and drug delivery. Among these nanoparticles, quantum dots (QDs) are highly appealing due to their manipulatable surfaces, yielding multifunctional QDs applicable in different biological models. The biocompatibility of these QDs, however, remains questionable.


RESULTS
We show here that QD surface modifications with N-acetylcysteine (NAC) alter QD physical and biological properties. In human neuroblastoma (SH-SY5Y) cells, NAC modified QDs were internalized to a lesser extent and were less cytotoxic than unmodified QDs. Cytotoxicity was correlated with Fas upregulation on the surface of treated cells. Alongside the increased expression of Fas, QD treated cells had increased membrane lipid peroxidation, as measured by the fluorescent BODIPY-C11 dye. Moreover, peroxidized lipids were detected at the mitochondrial level, contributing to the impairment of mitochondrial functions as shown by the MTT reduction assay and imaged with confocal microscopy using the fluorescent JC-1 dye.


CONCLUSIONS
QD core and surface compositions, as well as QD stability, all influence nanoparticle internalization and the consequent cytotoxicity. Cadmium telluride QD-induced toxicity involves the upregulation of the Fas receptor and lipid peroxidation, leading to impaired neuroblastoma cell functions. Further improvements of nanoparticles and our understanding of the underlying mechanisms of QD-toxicity are critical for the development of new nanotherapeutics or diagnostics in nano-oncology.
Choi
Angela O
AO
Department of Pharmacology & Therapeutics, McGill University, 3655 Promenade Sir William-Osler, McIntyre Medical Sciences Building, Montreal, QC, H3G 1Y6, Canada. angela.choi@mail.mcgill.ca
Cho
Sung Ju
SJ
Desbarats
Julie
J
Lovrić
Jasmina
J
Maysinger
Dusica
D