Dataset Information

Hypochlorous Acid-Activated UCNPs-LMB/VQIVYK Multifunctional Nanosystem for Alzheimer's Disease Treatment.

ABSTRACT: The development of nanosystems, which can photooxygenate amyloid-β (Aβ), detect the Tau protein, and inhibit effectively the Tau aggregation, is increasingly important in the diagnosis and therapy of Alzheimer's disease (AD). Herein, UCNPs-LMB/VQIVYK (UCNPs: upconversion nanoparticles, LMB: Leucomethylene blue, and VQIVYK: Biocompatible peptide) is designed as a HOCl-controlled released nanosystem for AD synergistic treatment. Under exposure to high levels of HOCl, the released MB from UCNPs-LMB/VQIVYK will produce singlet oxygen (¹O₂) under red light to depolymerize Aβ aggregation and reduce cytotoxicity. Meanwhile, UCNPs-LMB/VQIVYK can act as an inhibitor to decrease Tau-induced neurotoxicity. Besides, UCNPs-LMB/VQIVYK can be used for upconversion luminescence (UCL) due to its unexceptionable luminescence properties. This HOCl-responsive nanosystem offers a new therapy for AD treatment.

SUBMITTER: Qiao L

PROVIDER: S-EPMC10143957 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Hypochlorous Acid-Activated UCNPs-LMB/VQIVYK Multifunctional Nanosystem for Alzheimer's Disease Treatment.

Qiao Luying L Shen Yang Y Li Guangzhi G Lv Guanglei G Li Chunxia C

Journal of functional biomaterials 20230408 4

The development of nanosystems, which can photooxygenate amyloid-β (Aβ), detect the Tau protein, and inhibit effectively the Tau aggregation, is increasingly important in the diagnosis and therapy of Alzheimer's disease (AD). Herein, UCNPs-LMB/VQIVYK (UCNPs: upconversion nanoparticles, LMB: Leucomethylene blue, and VQIVYK: Biocompatible peptide) is designed as a HOCl-controlled released nanosystem for AD synergistic treatment. Under exposure to high levels of HOCl, the released MB from UCNPs-LMB ...[more]

PMID: 37103297

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Project description:BackgroundTargeted delivery of anticancer chemotherapeutics such as mitoxantrone (MTX) can significantly intensify their cytotoxic effects selectively in solid tumors such as breast cancer. In the current study, folic acid (FA)-armed and MTX-conjugated magnetic nanoparticles (MNPs) were engineered for targeted eradication of folate receptor (FR)-positive cancerous cells. Polyethylene glycol (PEG), FA and MTX were covalently conjugated onto the MNPs to engineer the PEGylated FA-MTX-MNPs. The internalization studies were performed using fluorescein isothiocyanate (FITC)-labeled FA-decorated MNPs (FA-FITC-MNPs) in both FR-positive MCF-7 cells and FR-negative A549 cells by means of fluorescence microscopy and flow cytometry. The cellular and molecular impacts of FA-MTX-MNPs were examined using trypan blue cell viability and FITC-labeled annexin V apoptosis assays and 4',6-diamidino-2-phenylindole (DAPI) staining, DNA ladder and quantitative polymerase chain reaction (qPCR) assays.ResultsThe FR-positive MCF-7 cells showed significant internalization of the FA-FITC-MNPs, but not the FR-negative A549 cells. The FR-positive cells treated with the PEGylated FA-MTX-MNPs exhibited the IC50 values of 3 ?g/mL and 1.7 ?g/mL, 24 h and 48 h post-treatment, respectively. DAPI staining and DNA ladder assays revealed significant condensation of nucleus and fragmentation of genomic DNA in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs as compared to the FR-negative A549 cells. The FITC-labeled annexin V assay confirmed emergence of late apoptosis (>80%) in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs, but not in the FR-negative A549 cells. The qPCR analysis confirmed profound cytotoxic impacts via alterations of apoptosis-related genes induced by MTX-FA-MNPs in MCF-7 cells, but not in the A549 cells.ConclusionOur findings evince that the engineered PEGylated FA-MTX-MNPs can be specifically taken up by the FR-positive malignant cells and effectively demolish them through up-regulation of Bcl-2-associated X protein (Bax) and Caspase 9 and down-regulation of AKt. Hence, the engineered nanosystem is proposed for simultaneous targeted imaging and therapy of various cancers overexpressing FRs.

Dataset Information

Hypochlorous Acid-Activated UCNPs-LMB/VQIVYK Multifunctional Nanosystem for Alzheimer's Disease Treatment.

Publications

Hypochlorous Acid-Activated UCNPs-LMB/VQIVYK Multifunctional Nanosystem for Alzheimer's Disease Treatment.

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