Heterojunction semiconductor nanocatalysts as cancer theranostics

Abstract

Cancer nanotechnology is a promising area of cross-disciplinary research aiming to develop facile, effective, and noninvasive strategies to improve cancer diagnosis and treatment. Catalytic therapy based on exogenous stimulus-responsive semiconductor nanomaterials has shown its potential to address the challenges under the most global medical needs. Semiconductor nanocatalytic therapy is usually triggered by the catalytic action of hot electrons and holes during local redox reactions within the tumor, which represent the response of nontoxic semiconductor nanocatalysts to pertinent internal or external stimuli. However, careful architecture design of semiconductor nanocatalysts has been the major focus since the catalytic efficiency is often limited by facile hot electron/hole recombination. Addressing these challenges is vital for the progress of cancer catalytic therapy. In recent years, diverse strategies have been developed, with heterojunctions emerging as a prominent and extensively explored method. The efficiency of charge separation under exogenous stimulation can be heightened by manipulating the semiconducting performance of materials through heterojunction structures, thereby enhancing catalytic capabilities. This review summarizes the recent applications of exogenous stimulus-responsive semiconducting nanoheterojunctions for cancer theranostics. The first part of the review outlines the construction of different heterojunction types. The next section summarizes recent designs, properties, and catalytic mechanisms of various semiconductor heterojunctions in tumor therapy. The review concludes by discussing the challenges and providing insights into their prospects within this dynamic and continuously evolving field of research.

SCHEME 1.

A schematic representation of the classification, stimuli, and modes of cancer treatment using heterojunction nanocatalysts.

FIG. 1.

Schematic of the charge transfer mechanisms in different heterojunctions adopted in the photo/sonocatalytic process. Four types (a) type I, (b) type II, (c) Z-scheme, and (d) Schottky junction are included. CB—conduction band, VB—valence band, and E_f—Fermi level.

FIG. 2.

(a) Possible photocatalytic redox reactions to produce/increase ROS for oxidative damage on cancer cells. (b) Schematic representation of Z‐scheme Bi₂S₃@Bi heterostructure and the possible mechanism underlying the generation of O₂ and ROS under NIR laser irradiation at 808 nm. Reproduced with the permission from Cheng et al., Adv. Mater. 32(11), 1908109 (2020). Copyright 2020 John Wiley and Sons. (c) Mechanism of Bi₂S₃-x-Au@HA (hyaluronic acid) for photocatalytic antitumor reactions against 4T1 tumor cells under 1064 nm NIR-II laser irradiation. Reproduced with the permission from Meng et al., J. Colloid Interface Sci. 644, 437–453 (2023). Copyright 2023 Elsevier. (d) The charge transfer mechanism and the generation of ROS in Bi-HA (humic acid)/FK866 heterojunction under NIR laser for effectively inhibiting NAD/ERK/NF-κB signal pathway and cancer cell migration. Reproduced with the permission from Song et al., Biomaterials 254, 120140 (2020). Copyright 2020 Elsevier. (e) The overall mechanisms of ROS generation and GSH depletion in Z-scheme BP@CPP heterojunctions for enhanced lipid peroxidation and amplified ferroptotic cell death. Reproduced with the permission from Liu et al., Small 20, 2309206 (2023). Copyright 2023 John Wiley and Sons.

FIG. 3.

(a) Schematic illustration of synthesis procedure of TiO₂@MnO_2-x-PEG nanosheets, HAADF-STEM image, and HR-TEM image of TiO₂@MnO_2-x nanosheets and 4T1 tumor photographs after different treatments. Reproduced with the permission from Zhou et al., Chem. Eng. J. 431, 134017 (2022). Copyright 2022 Elsevier. (b) Schematic illustration of synergistic sonocatalytic therapy of Pt-ZnO with triple ROS amplification effect for effective tumor therapy. Reproduced with the permission from Li et al., Acta Biomater. 171, 543–552 (2023). Copyright 2023 Elsevier. (c) Schematic illustration of a type II N-CD@LiFePO₄ heterojunction and the photocatalytic ROS generation mechanism and HRTEM image featuring the deposition of CD on the surface of LiFePO₄. Also shown is the relative cell viability of 143B cells treated with N-CD@LiFePO₄ + H₂O₂ under US irradiation. Reproduced with the permission from Hu et al., Chem. Eng. J. 446, 137320 (2022). Copyright 2022 Elsevier. (d) The proposed mechanism of enhanced sonodynamic performance, including GSH depletion, hypoxia alleviation, and photothermal effect of Bi@Bi₂O₃@Bi₂S₃-PEG NPs. Reproduced with the permission from Song et al., Adv. Healthcare Mater. 11(11), 2102503 (2022). Copyright 2022 John Wiley and Sons.

FIG. 4.

(a) Schematic representation of the generation of ROS under x-ray irradiation for radiocatalytic therapy using BiOI@Bi₂S₃ heterojunction NPs. Reproduced with the permission from Guo et al., Adv. Mater. 29(44), 1704136 (2017). Copyright 2017 John Wiley and Sons. (b) The possible charge transfer mechanism to generate cytotoxic free radicals in the tumor treatment by BiP₅W₃₀@rGO (PVP-PG) heterostructures under x-ray irradiation along with the in vitro ROS fluorescence imaging under different treatments. Reproduced with the permission from Zhou et al., Biomaterials 189, 11–22 (2019). Copyright 2019 Elsevier. (c) Illustration of possible charge transfer routes and the working principles of AuPt@CuS nanosheets to generate cytotoxic free radicals under x-ray irradiation for effective tumor therapy. Reproduced with the permission from Cai et al., J. Am. Chem. Soc. 143(39), 16113–16127 (2021). Copyright 2022 American Chemical Society. (d) Illustration of the combined radiotherapy and CuO@GDY-mediated radiocatalytic therapy and their effects on colony formation of 4T1 cells and HUVECs under various treatments. Reproduced with permission from Wang et al., ACS Nano 16(12), 21186–21198 (2022). Copyright 2022 American Chemical Society.

FIG. 5.

(a) Illustration of the resonance energy transfer process in Au@CuS NPs, in vitro western blot analysis of HSP70 and HO-1, thermal infrared images and H&E staining of Au@CuS NPs treated tumor. Reproduced with the permission from Chang et al., Nano Lett. 18(2), 886–897 (2018). Copyright 2018 American Chemical Society. (b) The FDTD simulation showing the electric field distributions of CuS and Pt-CuS under 808 nm laser irradiation for 7 min to reveal the mechanism of the photothermal effect along with experimental photothermal elevation profiles of CuS and Pt-CuS. Reproduced with the permission from Liang et al., Nano Lett. 19(6), 4134–4145 (2019). Copyright 2019 American Chemical Society. (c) Schematic illustration of photo/radiocatalytic ROS generation and immunogenic cell death for cancer immunotherapy by WO_2.9-WSe₂-PEG NPs under x-ray irradiation. Reproduced with the permission from Dong et al., ACS Nano 14(5), 5400–5416 (2020). Copyright 2020 American Chemical Society.

FIG. 6.

(a) Illustration of the charge transfer mechanism for catalytic ROS and H₂ generation by Bi/BiO_x lateral nano-heterostructure under normoxic and hypoxic conditions. Reproduced with the permission from Qiu et al., Adv. Mater. 33(49), 2102562 (2021). Copyright 2021 John Wiley and Sons. (b) Photocatalytic mechanism of visible light driven combinatorial H₂ therapy and cuproptosis by Cu@CDCN nanosheets. Reproduced with the permission from Ding et al., Angew. Chem., Int. Ed. 62(44), 202311549 (2023). Copyright 2023 John Wiley and Sons. (c) Sonocatalytic charge transfer mechanism in Z-scheme FeOCl/FeOOH nanosheets for O₂ generation and H₂O₂ generation for effective Fenton-like reaction. Reproduced with the permission from Kang et al., Nat. Commun. 13(1), 2425 (2022). Copyright 2022 Authors, licensed under Creative Commons Attribution (CC BY) license. (d) Schematic representation of photocatalytic mechanism in FeS₂/CoS₂@PEG nanosheets for the production of O₂ in combination with PTT/PDT/CDT and immunotherapy for effective tumor treatment. Reproduced with the permission from Wang et al., J. Colloid Interface Sci. 625, 145–157 (2022). Copyright 2022 Elsevier. (e) TEM image and HR TEM image of BiOBr@Bi₂S₃ showing the close contact of BiOBr and Bi₂S₃ nanorod for the effective formation of heterojunction. Reproduced with the permission from Yuan et al., Adv. Sci. 11, 2308546 (2024). Copyright 2024 John Wiley and Sons.