Journal
HELIYON
Volume 9, Issue 9, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.heliyon.2023.e20028
Keywords
Quantum dots; Polyethylene glycol modification; Cellular uptake; Intracellular behavior; Sub-acute cytotoxicity
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This study established a cell model representing the circulatory system to investigate the cellular internalization and cytotoxicity of 6-arm PEG-amine/mPEG QDs. The results showed low cellular uptake of QDs, preservation in the Golgi apparatus, minimal acute cytotoxicity, and sub-acute cytotoxicity caused by elevated ROS generation.
Quantum Dots (QDs) modified with branched Polyethylene Glycol-amine (6-or 8-arm PEG -amine) coupled with methoxy PEG (mPEG) hold great promise for in vivo biomedical applica-tions due to a long half-life in blood and negligible toxicity. However, the potential risks regarding their concomitant prolonged co-incubation with cardiovascular and blood cells remains inconclusive. In the present study, the feasible, effective and convenient proliferating-restricted cell line models representing the circulatory system were established to investigate the cellular internalization followed by intracellular outcomes and resulting acute/sub-acute cytotoxicity of the 6-arm PEG-amine/mPEG QDs. We found a dose-, time-and cell type-dependent cellular up-take of the 6-arm PEG-amine/mPEG QDs, which was ten-fold lower compared to the traditional linear PEG-modified counterpart. The QDs entered cells via multiple endocytic pathways and were mostly preserved in Golgi apparatus for at least one week instead of degradation in lyso-somes, resulting in a minimal acute cytotoxicity, which is much lower than other types of PEG -modified QDs previously reported. However, a sub-acute cytotoxicity of QDs were observed several days post exposure using the concentrations eliciting no-significant acute cytotoxic ef-fects, which was associated with elevated ROS generation caused by QDs remained inside cells. Finally, a non-cytotoxic concentration of the QDs was identified at the sub-acute cytotoxic level. Our study provided important information for clinical translation of branched PEG-amine/mPEG QDs by elucidating the QDs-cell interactions and toxicity mechanism using the proliferation -restricted cell models representing circulatory system. What's more, we emphasized the indis-pensability of sub-acute cytotoxic effects in the whole biosafety evaluation process of nano -materials like QDs.
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