Enhanced neuroprotective effect of verapamil-loaded hyaluronic acid modified carbon quantum dots in an in-vitro model of amyloid-induced Alzheimer's disease

• Published in: International journal of biological macromolecules Vol. 275; no. Pt 2; p. 133742
• Main Authors: Mosalam, Esraa M., Abdel-Bar, Hend Mohamed, Elberri, Aya Ibrahim, Abdallah, Mahmoud S., Zidan, Abdel-Aziz A., Batakoushy, Hany A., Abo Mansour, Hend E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2024
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Animals; Carbon - chemistry; Carbon - pharmacology; Carbon quantum dots; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Humans; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; Membrane Potential, Mitochondrial - drug effects; Neuroblastoma; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Quantum Dots - chemistry; Reactive Oxygen Species - metabolism; Verapamil; Verapamil - pharmacology; Verapamil; Carbon quantum dots; Neuroblastoma
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.133742

This study aims to investigate the molecular mechanisms and the neuroprotective effect of hyaluronic acid modified verapamil-loaded carbon quantum dots (VRH-loaded HA-CQDs) against an in-vitro Alzheimer's disease model induced by amyloid beta (Aβ) in SH-SY5Y and Neuro 2a neuroblastoma cells. Briefly, different HA-CQDs were prepared using hydrothermal method and optimized by Box-Behnken design to maximize quantum yield and minimize particle size. Serum stable negatively charged VRH-loaded HA-CQDs was successfully prepared by admixing the optimized HA-CQDs and VRH with association efficiency and loading capacity of 81.25 ± 3.65 % and 5.11 ± 0.81 %, respectively. Cells were pretreated with VRH solution or loaded-HA-CQDs followed by exposure to Aβ. Compared to the control group, amyloidosis led to reduction in cellular proliferation, mitochondrial membrane potential, expression of cytochrome P450, cytochrome c oxidase, CREB-regulated transcriptional coactivator 3, and mitotic index, along with marked increase in reactive oxygen species (ROS) and inflammatory cytokines. Pretreatment with VRH, either free or loaded HA-CQDs, enhanced cell survival, mitochondrial membrane potential, mitotic index, and gene expression. It also reduced inflammation and ROS. However, VRH-loaded HA-CQDs exhibited superior effectiveness in the measured parameters. These findings suggest that VRH-loaded HA-CQDs have enhanced therapeutic potential compared to free VRH in mitigating amyloidosis negative features.
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