Vacancy defect-promoted nanomaterials for efficient phototherapy and phototherapy-based multimodal Synergistic Therapy

Abstract

Phototherapy and multimodal synergistic phototherapy (including synergistic photothermal and photodynamic therapy as well as combined phototherapy and other therapies) are promising to achieve accurate diagnosis and efficient treatment for tumor, providing a novel opportunity to overcome cancer. Notably, various nanomaterials have made significant contributions to phototherapy through both improving therapeutic efficiency and reducing side effects. The most key factor affecting the performance of phototherapeutic nanomaterials is their microstructure which in principle determines their physicochemical properties and the resulting phototherapeutic efficiency. Vacancy defects ubiquitously existing in phototherapeutic nanomaterials have a great influence on their microstructure, and constructing and regulating vacancy defect in phototherapeutic nanomaterials is an essential and effective strategy for modulating their microstructure and improving their phototherapeutic efficacy. Thus, this inspires growing research interest in vacancy engineering strategies and vacancy-engineered nanomaterials for phototherapy. In this review, we summarize the understanding, construction, and application of vacancy defects in phototherapeutic nanomaterials. Starting from the perspective of defect chemistry and engineering, we also review the types, structural features, and properties of vacancy defects in phototherapeutic nanomaterials. Finally, we focus on the representative vacancy defective nanomaterials recently developed through vacancy engineering for phototherapy, and discuss the significant influence and role of vacancy defects on phototherapy and multimodal synergistic phototherapy. Therefore, we sincerely hope that this review can provide a profound understanding and inspiration for the design of advanced phototherapeutic nanomaterials, and significantly promote the development of the efficient therapies against tumor.

Keywords: microstructure; multimodal synergistic phototherapy; nanophotosensitizers; phototherapy; vacancy defect engineering.

SCHEME 1

Schematic illustration of vacancy defect-promoted nanomaterials for efficient phototherapy and multimodal synergistic phototherapy.

FIGURE 1

(A) Schematic of various defects in crystals. Reproduced with permission from Xie et al. (2020). Copyright © 2020 American Chemical Society. (B) Illustrations of O₂ adsorption on partially reduced TiO₂ surface to form •O₂ ⁻ (adsorbed type A) and O₂ adsorption on oxygen vacancy defective TiO₂ surface to form •O₂ ⁻ under light irradiation (adsorbed type B). Reproduced with permission from Komaguchi et al. (2010). Copyright © 2010 American Chemical Society. (C) Schematic density of states for TiO₂ P25 Degussa (black dotted line) and black TiO₂ nanoparticle with oxygen vacancies (red line), Vo represents the localized states created by oxygen vacancies in black TiO₂ nanoparticle; illustration of the microstructure of black TiO₂ nanoparticle with oxygen vacancies, Vo represents the oxygen vacancy. Reproduced with permission from Naldoni et al. (2012). Copyright © 2012 American Chemical Society. (D) NIR spectra of Cu vacancy defective Cu_2−xS. Reproduced with permission from Zhao et al. (2009). Copyright © 2009 American Chemical Society.

FIGURE 2

(A) Schematic illustration of the preparation of ultrathin MnO₂ nanosheets with abundant oxygen vacancies through hydrothermal method. Reproduced with permission from Wang L. et al. (2019). Copyright © 2019 American Chemical Society. (B) Illustration of the formation process of oxygen vacancies in Ce-doped Aurivillius Bi₂MoO₆ structure. Reproduced with permission from Dai et al. (2016). Copyright © 2016 American Chemical Society.

FIGURE 3

(A) Schematic diagram of Na_xGdWO₃ nanorods for MRI-guided photothermal, TEM images of Na_xGdWO₃ nanorods, and in vivo T ₁-weighted MR images of 4T1-tumor-bearing mice before and after (I)T. injection of Na_xGdWO₃ nanorods. Reproduced with permission from Ni et al. (2017). Copyright © 2017 American Chemical Society. (B) Schematic illustration of geometric structure of various BiOBr-based samples and Rub₂d sample, band structures of BiOBr and BiOBr–H, and the band edge positions of BiOBr, BiOBr–H and Rub₂d. Reproduced with permission from Guan et al. (2019). Copyright © 2019 The Royal Society of Chemistry.

FIGURE 4

Illustration on action mechanism of B-TiO_2−x for synergetic PTT and PDT, geometric-phase analysis (GPA) of B-TiO_2−x (white arrows indicate the position of atomic dislocations), calcein AM and PI co-staining of B16F10 melanoma cells after the treatment with B-TiO_2−x and NIR irradiation, infrared thermal images of B16F10 tumor-bearing mice after various treatments, and representative photographs of the dissected tumors. Reproduced with permission from Wang X. et al. (2019). Copyright © 2019 American Chemical Society.

FIGURE 5

STEM image of AuPt@CuS NSs, schematic illustration of enhanced photothermal mechanism of AuPt@CuS NSs, proposed mechanism of the enhanced deposition of radiation energy by AuPt@CuS NSs, tumor growth curves of 4T1 tumor-bearing mice after various treatments, representative photographs of the dissected tumors, and evaluation of dual modal CT/PA bioimaging capability of T80-AuPt@CuS NSs. Reproduced with permission from Cai et al. (2021). Copyright © 2021 American Chemical Society.

FIGURE 6

Schematic Illustration of the synthesis of CoFe-500 for PA/MR/NIR imaging-guided PTT, Fourier-transform EXAFS spectra at Co K-edge for various CoFe-x samples, Co 2p XPS spectra for CoFe-500 and CoFe-800, Co²⁺ defect/Co²⁺ peak area ratio for various CoFe-x samples, and optimized geometries for a CoFe-500 bulk heterojunction composed of CoO-V_Co and CoFe₂O₄-V_Co, band structures of CoO-V_Co and CoFe₂O₄-V_Co, 3D PAI images of tumor site at 6 h postinjection, in vivo T1-MRI imaging of HeLa-bearing mice before and after injected with CoFe-500, and photographs at different times after various treatments. Reproduced with permission from Wang L. et al. (2021). Copyright © 2020 American Chemical Society.