Functionalized Upconversion Nanoparticles for Disassembly of β‑Amyloid Aggregation with Near-Infrared Excitation
Received date: 2021-05-06
Online published: 2021-06-09
Supported by
National Natural Science Foundation of China(21807028); National Natural Science Foundation of China(21625503)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, confusion, and a variety of cognitive disabilities. The self-assembly and aggregation of β-amyloid (Aβ) peptides is a main feature of the brain of Alzheimer's disease, which can aggravate the nerve damage and cognitive impairment of AD patients. Therefore, inhibition of the aggregation of Aβ peptides is recognized as a potential strategy to alleviate AD. Photodynamic therapy (PDT) is a creative method that has wide applications in suppressing amyloid aggregation or eliminating the amyloid aggregates. However, most photosensitizers are excited by ultraviolet and visible light, have a low penetration depth in biological tissues, and cause serious tissue damage, which limits their application in biomedicine. Herein, we report a dual-targeting upconversion nanoprobe excited by near-infrared light to inhibit the Aβ aggregation process. The core-shell structured upconversion nanoparticles NaYF4:Yb,Er,Gd,Tm@NaYF4 are used as light converters, and the photosensitizer chlorin-e6 (Ce6) is loaded through the hydrophobic coating of the amphiphilic polymer 1,2-distearoylsn-glycero-3-phosphoethanolamine-N- [maleimide(polyethyleneglycol)-2000] (DSPE-PEG-MAL). A blood-brain barrier targeting peptide, TGN, and a Aβ target peptide, QSH, are simultaneously modified on the surface of nanoparticles via the specific reaction between maleimide and sulfhydryl groups. The results indicate that UCNPs can transfer the excited-state energy to the photosensitizer Ce6 through luminescence resonance energy transfer (LRET) process under the excitation of near-infrared light irradiation. After transition to the excited state, Ce6 further interact with the surrounding oxygen molecules to produce singlet oxygen (1O2) and irreversibly oxidize β-amyloid, thus effectively disassembling Aβ aggregates and reducing the cytotoxicity associated with Aβ. In addition, UCNPs-Ce6-TQ not only exhibits good biocompatibility, but also can effectively cross the blood-brain barrier and target Aβ42. This nanoprobe may be a powerful tool to inhibit the accumulation of Aβ in the brain and alleviate the neurotoxic damage caused by Aβ.
Ju Huang , Zhen Li , Zhihong Liu . Functionalized Upconversion Nanoparticles for Disassembly of β‑Amyloid Aggregation with Near-Infrared Excitation[J]. Acta Chimica Sinica, 2021 , 79(8) : 1049 -1057 . DOI: 10.6023/A21050194
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