Engineered 2D materials for optical bioimaging and path toward therapy and tissue engineering

Abstract

Two-dimensional (2D) layered materials as a new class of nanomaterial are characterized by a list of exotic properties. These layered materials are investigated widely in several biomedical applications. A comprehensive understanding of the state-of-the-art developments of 2D materials designed for multiple nanoplatforms will aid researchers in various fields to broaden the scope of biomedical applications. Here, we review the advances in 2D material-based biomedical applications. First, we introduce the classification and properties of 2D materials. Next, we summarize surface and structural engineering methods of 2D materials where we discuss surface functionalization, defect, and strain engineering, and creating heterostructures based on layered materials for biomedical applications. After that, we discuss different biomedical applications. Then, we briefly introduced the emerging role of machine learning (ML) as a technological advancement to boost biomedical platforms. Finally, the current challenges, opportunities, and prospects on 2D materials in biomedical applications are discussed.

Keywords: 2D materials; Biomedical applications; Machine learning; Surface engineering.

Figure 1

Schematic representation of synthesis and preparation, materials engineering, biomedical applications, and ML approaches applicable in 2D materials.

Figure 2

Schematic representation of surface functionalization in 2D materials. (a) PEGylation of GO by PEG stars. Adapted with permission from Reference [18] © 2008 Springer. (b) Graphene-PLL Synthesis. Adapted with permission from Reference [60] © 2009 American Chemical Society. (c) Synthesis of lanthanide-coordinated BP nanosheets. Adapted with permission from Reference [65] © 2018 Wiley Online Library. (d) Solvothermal synthesis procedure of MoS₂-PEG nanosheets. Adapted with permission from Reference [69] © 2015 Elsevier. (e) Synthesis procedure of WS₂ nanosheets and their application as a multifunctional photosensitizer delivery system. Adapted with permission from Reference [72] © 2014 Royal Society of Chemistry. (f) Liquid-phase exfoliation of BP nanosheets and their surface modification with PLL. Adapted with permission from Reference [68] © 2016 American Chemical Society. (g) Exfoliation and PEGylation of WS₂ nanosheets. Adapted with permission from Reference [17] © 2013 Wiley Online Library.

Figure 3

Illustration of structural-engineering approaches. (a) Schematic illustration of defect state in WSe₂ monolayer. Adapted with permission from Reference [83] © 2022 Springer Nature Limited. (b) Defect creation from Focus Ion Beam. Adapted with permission from Reference [81] © 2020 Royal Society of Chemistry. (c) Defect creation from plasma treatment. (d) Defect-assisted PL enhancement in monolayer MoS₂ after thermal treatment. Adapted with permission from Reference [87] © 2014 AIP Publishing. (e) Detection of DNA using MoS₂/graphene heterostructure, adapted with permission from Reference [101] © 2014 Wiley Online Library. (f) Schematic of MoS₂/graphene-enhanced SPR biosensor. Adapted with permission from Reference [102] © 2014 Elsevier. (g) Enhanced Radiotherapy and PTT by using Metal-ion-doped WS₂. Adapted with permission from Reference [105] © 2015 American Chemical Society.

Figure 4

Different bioimaging modalities applicable in 2D materials. (a) Serial coronal PET images at different time points post-injection of ⁶⁴Cu-RGO-PEG, ⁶⁴Cu-NOTA-PEG-RGO, and (⁶⁴Cu-NOTA)-rGO-PEG acquired in 4T1 tumor-bearing mice. Adapted with permission from Reference [111] © 2017 Wiley Online Library. (b), (c), and (d) Schematic illustration of theranostic functions of MnO_x/Ti₃C₂–SP composite nanosheets, in vitro T₁-weighted MR imaging of MnO_x/Ti₃C₂–SP nanosheets in buffer solution at different pH values, and T₁-weighted imaging at different time intervals. Adapted with permission from Reference [115] © 2017 American Chemical Society.

Figure 5

Different drug and gene delivery pathways based on 2D materials. (a) Schematic illustrating the making of MTX-loaded SA-CA²⁺-GO hybrids. Adapted with permission from Reference [132] © 2020 Elsevier. (b) Preparation of rGO/DA/AuNP/DOX hybrid nanomaterial with pH-dependent DOX drug release Adapted with permission from Reference [134] © 2022 Elsevier. (c) Synthesis of Lf-GO-Pue hybrid for targeted treatment of PD. Adapted with permission from Reference [135] © 2021 Royal Society of Chemistry. (d) Schematic illustration of MoS₂ NDs-incorporated MSN for pH-sensitive drug delivery and CT imaging. Adapted with permission from Reference [137] © 2021 Elsevier. (e) Surface modification of Ti₃C₂ nanosheets by SP, their further DOX drug loading, and responsive drug releasing by external irradiation or internal pH change. Adapted with permission from Reference [78] © 2018 Wiley. (f) Anti-tumor activity of multifunctionalized PEG-GO nanomaterial with representative tumor tissue images of mice treated with (1) PBS, (2) FA/GO/scramble siRNA, (3) FA/GO with NIR light, (4) FA/GO/(H + K) siRNA, or (5) FA/GO/(H + K) siRNA with NIR light. Adapted with permission from Reference [147] © 2017 Ivyspring International. (g) Relative changes in tumor volume over time after mice treated with multifunctionalized PEG-GO nanomaterial. Adapted with permission from Reference [147] © 2017 Ivyspring International. (h) Schematic illustration for combined PT and gene delivery for human ovarian cancer cells using BPQD-PAH loaded with siRNA. Adapted with permission from Reference [148] © 2017 Royal Society of Chemistry.

Figure 6

Various applications of 2D materials in PTT. (a) Schematic illustration of synthesis and theranostic functions of MnO_x/Ta₄C₃–SP composite nanosheets. Adapted with permission from Reference [77] © 2017 American Chemical Society. (b) PT heating curves of pure water and Ti₃C₂@Au nanocomposites with various concentrations. Adapted with permission from Reference [76] © 2019 American Chemical Society. (c) Typical photograph and (d) Tumor growth curves of the MCF7 breast tumor-bearing nude mice irradiated by the 808 nm and 1.5 W cm⁻² NIR laser for 10 min after intravenous injection of bare BPs and NB@BPs. Adapted with permission from Reference [62] © 2017 American Chemical Society. (e) Schematic illustration of the theranostic function of Ti₃C₂@Au. Adapted with permission from Reference [76] © 2017 American Chemical Society. (f) IR thermal images of 4T1 tumor-bearing nude mice with or without intravenous injection of MnO_x/Ta₄C₃–SP nanosheets. Adapted with permission from Reference [77] © 2017 American Chemical Society.

Figure 7

Various tissue engineering applications in 2D materials. (a) Scanning electron microscopy images and frequency distribution of the fiber diameter for PVPA–ESM composites with no rGO, 0.5 wt% rGO, 1 wt% rGO, and 2 wt% rGO fibers, respectively. Adapted with permission from Reference [164] © 2021 MDPI. (b) Cell viability of PVPA–ESM/x wt% rGO nanofibers with various rGO concentrations (x = 0, 0.5, 1 ,and 2 wt%). Adapted with permission from Reference [164] © 2021 MDPI. (c) Surface potential distribution from KFPM for PHB and PHB-rGO single fibers on the surface of ITO-PET substrates. Vertical and lateral PFM images of the fibers. Adapted with permission from Reference [165] © 2021 Elsevier. (d) Schematic showing the BP nanosheet based 3D hydrogel scaffold for effective bone regeneration. Adapted with permission from Reference [169] © 2019 American Chemical Society. (e) CT scan images showing bone regeneration performance in the control group, MXene group and HA/MXene group at 4 and 8 weeks after surgery. Adapted with permission from Reference [173] © 2021 Elsevier.

Figure 8

Illustration of applicability of ML in materials science and biomedical applications. (a) General process of ML-based data analysis. Adapted with permission from Reference [16] © 2020 American Chemical Society. (b) Benefits of ML brought to biosensors. Adapted with permission from Reference [16] © 2020 American Chemical Society. (c) Structural models of bulk MAX phase (upper right) and the corresponding MXene highlighted in pinks. Word clouds (lower right) where large (small) font size and red (orange) color correspond to high (low) predicted synthesizability of the named compound. Adapted with permission from Ref. [189] © 2019 American Chemical Society. (d) ML tasks in NP synthesis. In predictions tasks, ML predicts NP properties based on experimental conditions. Adapted with permission from Ref. [190] © 2021 Springer Nature Limited. (e) In experiment-planning tasks, ML proposes new experiments to find an optimal set of conditions that result in NP with the desired properties. Adapted with permission from Ref. [190] © 2021 Springer Nature Limited.