A biomimetic upconversion nanoreactors for near-infrared driven H2 release to inhibit tauopathy in Alzheimer's disease therapy

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2024-08-30 DOI:10.1016/j.bioactmat.2024.08.029

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Abstract

Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders, such as Alzheimer's disease (AD), which can be induced by an excess of reactive oxygen species (ROS). As an antioxidant, hydrogen gas (H₂) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH. However, conventional administration methods of H₂ face significant challenges in controlling H₂ release on demand and fail to achieve effective accumulation at lesion sites. Herein, we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared (NIR) light-driven photocatalytic H₂ evolution in situ. The nanoreactors are constructed by biocompatible crosslinked vesicles (CVs) encapsulating ascorbic acid and two photosensitizers, chlorophyll a (Chla) and indoline dye (Ind). In addition, platinum nanoparticles (Pt NPs) serve as photocatalysts and upconversion nanoparticles (UCNP) act as light-harvesting antennas in the nanoreacting system, and both attach to the surface of CVs. Under NIR irradiation, the nanoreactors release H₂ in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model. Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.

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一种用于近红外驱动 H2 释放的生物仿生上转换纳米反应器，可抑制阿尔茨海默病治疗中的牛磺酸病变

tau 蛋白的异常过度磷酸化是阿尔茨海默病（AD）等神经退行性疾病发病的一个主要病理标志，过量的活性氧（ROS）可诱发这种疾病。作为一种抗氧化剂，氢气（H2）有可能通过清除高度有害的 ROS（如-OH）来缓解阿尔茨海默病。然而，传统的氢气施用方法在控制氢气按需释放方面面临巨大挑战，而且无法在病变部位实现有效积累。在此，我们报告了模仿自然光合作用的人工纳米反应器，以实现近红外（NIR）光驱动的光催化 H2 原位进化。这种纳米反应器由生物相容性交联囊泡（CVs）构建而成，其中封装了抗坏血酸和两种光敏剂--叶绿素a（Chla）和吲哚啉染料（Ind）。此外，铂纳米粒子（Pt NPs）作为光催化剂，上转换纳米粒子（UCNP）作为纳米反应系统中的光收集天线，都附着在 CVs 表面。在近红外照射下，纳米反应器会在原位释放出 H2，清除局部过量的 ROS，减轻 AD 小鼠模型中 tau 的过度磷酸化。这种近红外触发的纳米反应器提供了一种概念验证设计，证明了氢气疗法在抗抑郁性痴呆症方面的巨大潜力。

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.