Recent advances in two-dimensional materials for the diagnosis and treatment of neurodegenerative diseases

Abstract

With the size of the aging population increasing worldwide, the effective diagnosis and treatment of neurodegenerative diseases (NDDs) has become more important. Two-dimensional (2D) materials offer specific advantages for the diagnosis and treatment of NDDs due to their high sensitivity, selectivity, stability, and biocompatibility, as well as their excellent physical and chemical characteristics. As such, 2D materials offer a promising avenue for the development of highly sensitive, selective, and biocompatible theragnostics. This review provides an interdisciplinary overview of advanced 2D materials and their use in biosensors, drug delivery, and tissue engineering/regenerative medicine for the diagnosis and/or treatment of NDDs. The development of 2D material-based biosensors has enabled the early detection and monitoring of NDDs via the precise detection of biomarkers or biological changes, while 2D material-based drug delivery systems offer the targeted and controlled release of therapeutics to the brain, crossing the blood-brain barrier and enhancing treatment effectiveness. In addition, when used in tissue engineering and regenerative medicine, 2D materials facilitate cell growth, differentiation, and tissue regeneration to restore neuronal functions and repair damaged neural networks. Overall, 2D materials show great promise for use in the advanced treatment of NDDs, thus improving the quality of life for patients in an aging population.

Keywords: Drug delivery; Early diagnosis; Neurodegenerative disease; Regenerative medicine; Two-dimensional (2D) material.

Fig. 1

Schematic illustration of application of 2D nanomaterial for neurodegenerative disease

Fig. 2

Graphene-based biosensors for the diagnosis of neurodegenerative diseases (NDDs). a electrochemical biosensor which employs a dual-signal approach alongside Exo III-assisted recycling and the selective adsorption characteristics of graphene for identifying the trinucleotide repeat sequence d(CAG)n. Reproduced with permission and copyright (2019) Elsevier B.V. [45]. b Graphene-based field-effect transistor (gFET) for multiplex detection of Aβ1-42 and t-Tau using specific antibody-modified reduced graphene oxide. Reproduced with permission and copyright (2020) Elsevier B.V. [49]

Fig. 3

MXene-based biosensors for the diagnosis of NDDs. a Preparation of MXene-electrochemically reduced holey graphene (ERHG) on a glass carbon electrode and its antifouling process for dopamine sensing in complex biological fluids. Reproduced with permission and copyright (2022) Elsevier B.V. [53]. b Illustration of electrochemical determination of Aβ1-42 oligomers with the Au-MXene substrate and the aptamer/toluidine blue-Au@covalent organic frameworks (Apt/TB-Au@COFs). Reproduced with permission and copyright (2024) Elsevier B.V. [54]. c Schematic diagram of the AβO recognition strategy based on FRET technology and the microfluidic chip with a sandwich-like structure. Reproduced with permission and copyright (2022) American Chemical Society [41]. d Crack-propagation sensing mechanism using Nacre-inspired PAM-MXene nanocomposites induced by the nacre-mimetic “brick-and-mortar” architecture and the abundant hydrogen bond interfacial interactions. Reproduced with permission and copyright (2023) American Chemical Society [58]

Fig. 4

TMD-based biosensors for the diagnosis of NDDs. a all-integrated electrochemical sensor fabricated on a polyimide (PI) sheet with Mn-MoS₂ electrode and the quantification of DA. Reproduced with permission and copyright (2020) AAAS [62]. b Sensing mechanism and quantification data for miR-29a detection on the aptamer-modified WS₂ interface using quenching of the fluorescence of FAM-DNA. Reproduced with permission and copyright (2020) Elsevier B.V. [64]

Fig. 5

Graphene-based therapeutic strategies for NDDs treatment. a Developed graphene quantum dot (GQD)-assisted prevention of amyloid fibrils accumulation. Fused in sarcoma (FUS) could be phase separation to form liquid-like droplets. Reproduced with permission and copyright (2023) American Chemical Society [75]. b The microfluidic device was designed and fabricated for the synthesis of GQDs, chitosan (CS) nanoparticle, and GQD/CS for drug delivering agents against AD. Reproduced with permission and copyright (2023) Wiley-VCH. [77]. c Graphene oxide (GO)-based nanocapsules with photo-triggered drug released ability for implantable clear cell renal cell carcinoma (ccRCC) or neurodegeneration therapy. Reproduced with permission and copyright (2022) Elsevier B.V. [81]

Fig. 6

MXene-based therapeutic strategies for NDDs treatment. a 2D niobium carbide MXenzyme with multiple enzyme-mimicking activities to catalyze anti-inflammatory response and ROS scavenging. Reproduced with permission and copyright (2023) American Chemical Society [87]. b 2D niobium carbide MXenzyme under NIR-II irradiation to capture superfluous Cu²⁺ with high BBB permeability. Reproduced with permission and copyright (2022) Wiley-VCH. [88]

Fig. 7

TMD-based therapeutic strategies for NDDs treatment. a PCM/WS₂QDs@AuNC for serial activation of therapy and monitoring modules by activating second near-infrared laser. Reproduced with permission and copyright (2023) Elsevier B. V. [95]. b Stimulus-responsive TMD-based nanocomplex, UiO-66-NH₂@l-MoS₂ QDs@PA-Ni (MSP-U), for the treatment of AD by using decomposition of the formed Aβ plaque. Reproduced with permission and copyright (2023) Wiley-VCH. [100]