Acta Chimica Sinica ›› 2021, Vol. 79 ›› Issue (8): 1049-1057.DOI: 10.6023/A21050194 Previous Articles     Next Articles

Article

近红外光激发功能化上转换纳米颗粒用于解聚Aβ聚集体

黄菊a, 李贞b,*(), 刘志洪a,b,*()   

  1. a 武汉大学 化学与分子科学学院 武汉 430072
    b 湖北大学 化学化工学院 武汉 430062
  • 投稿日期:2021-05-06 发布日期:2021-06-09
  • 通讯作者: 李贞, 刘志洪
  • 基金资助:
    国家自然科学基金(21807028); 国家自然科学基金(21625503)

Functionalized Upconversion Nanoparticles for Disassembly of β‑Amyloid Aggregation with Near-Infrared Excitation

Ju Huanga, Zhen Lib(), Zhihong Liua,b()   

  1. a College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China
    b College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China
  • Received:2021-05-06 Published:2021-06-09
  • Contact: Zhen Li, Zhihong Liu
  • 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.

Key words: near infrared, upconversion nanoparticles, photodynamic therapy, beta-amyloid, Alzheimer's disease