Recent Advances in Single Fe-Based Nanoagents for Photothermal-Chemodynamic Cancer Therapy

Abstract

Monomodal cancer therapies are often unsatisfactory, leading to suboptimal treatment effects that result in either an inability to stop growth and metastasis or prevent relapse. Thus, synergistic strategies that combine different therapeutic modalities to improve performance have become the new research trend. In this regard, the integration of photothermal therapy (PTT) with chemodynamic therapy (CDT), especially PTT/CDT in the second near-infrared (NIR-II) biowindow, has been demonstrated to be a highly efficient and relatively safe concept. With the rapid development of nanotechnology, nanoparticles can be designed from specific elements, such as Fe, that are equipped with both PTT and CDT therapeutic functions. In this review, we provide an update on the recent advances in Fe-based nanoplatforms for combined PTT/CDT. The perspectives on further improvement of the curative efficiency are described, highlighting the important scientific obstacles that require resolution in order to reach greater heights of clinical success. We hope this review will inspire the interest of researchers in developing novel Fe-based nanomedicines for multifunctional theranostics.

Keywords: Fe-based nanoplatforms; chemodynamic therapy; photothermal therapy; second near-infrared biowindow; synergetic performance.

Figure 6

(A) Scheme of synthetic process of FPS-PVP nanosheets and their applications for synergistic CDT and PTT in the NIR-II biowindow. Inset is the ball-and-stick model of FPS. Reprinted with permission from Ref. [70]. Copyright 2020, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (B) The photoabsorption and photothermal effect of Cu_xFe_yS_z nanomaterials can be tuned by changing the Cu/Fe ratios, and Cu₅FeS₄ can be used as an efficient ‘‘one-for-all” type agent for MR imaging-guided photothermal-enhanced CDT. Reprinted with permission from Ref. [73]. Copyright 2021, Elsevier Inc. (C) Schematic illustration of the preparation of CuFe₂S₃-PEG nanosheets for efficient NIR-II PTT and CDT. Reprinted with permission from Ref. [74]. Copyright 2021, Elsevier Inc.

Figure 1

(A) Schematic illustrating the synthesis of BSA-CuFeS₂ nanoparticles and their applications for synergetic pH-independent CDT/PTT. (B) Transmission electron microscope (TEM) image of the BSA-CuFeS₂ NPs. (C) Photothermal effect of the BSA-CuFeS₂ aqueous suspensions ([Cu] = 100 ppm) under irradiation, and then the laser was shut off (808 nm laser, 1 W cm⁻²). (D) Calculation of the time constant (τ_s) and PCE. (E) UV−vis spectra of the 3,3,5,5-tetramethylbenzidine (TMB) aqueous with or without H₂O₂ or BSA-CuFeS₂ at varying pH values. BSA-CuFeS₂ with H₂O₂ could catalyze the reaction of TMB to cause a blue color reaction at varying pH conditions with maximum absorbance at 652 nm. Inset: corresponding different color reactions of samples. (F) T₂-weighted MR images of mice bearing transplanted 4T1 tumors injected intravenously with BSA-CuFeS₂ (15 mg kg⁻¹). (G) Biodistribution of Cu in the major organs at varying times. (H) Tumor growth volume curves after different treatments. Reprinted with permission from Ref. [60]. Copyright 2019, American Chemical Society.

Figure 2

Schematic depicting the synthesis of FMO nanowires and demonstrating FMO for photothermal enhanced CDT and GSH-depleted amplified CDT. Reprinted with permission from Ref. [61]. Copyright 2021, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 3

(A) Schematic detailing synthesis of the FeEP nanoplatform and illustrating its applications for mild PTT-enhanced CDT to promote tumor ablation. (B) Thermal images of FeEP with different concentrations (µg mL⁻¹) under 808 nm laser irradiation (1 W cm⁻², 15 min). (C) Fitted linear relationship between −ln θ and time. (D) UV-vis absorbance spectra of tetramethylbenzidine (TMB), H₂O₂ + TMB, FeEP + TMB and FeEP + H₂O₂ + TMB. (E) UV-vis absorbance of TMB at the wavelength of 652 nm after being co-incubated with FeEP and H₂O₂ together with and without laser irradiation. (F) UV-vis absorbance of TMB at the wavelength of 652 nm after incubation with Fe II + H₂O₂ or Fe II + H₂O₂ + EGCG. (*) p < 0.05, (**) p < 0.01 and (***) p < 0.001. (G) PA images of the tumor region from 4T1 tumor-bearing mice before and after intravenous injection of FeEP. (H) The relative HSP 90 expression level in 4T1 cells with different treatments. (I) The growth curves of tumor volumes of the mice after various treatments. (*) p < 0.05, (**) p < 0.01 and (***) p < 0.001. (J) Digital photography of the excised tumors from different mouse groups. Reprinted with permission from Ref. [63]. Copyright 2021, Elsevier Inc.

Figure 4

Schematic illustrating the fabrication and anti-tumor effect of FeS₂@RBCs in vivo. With RBCs coating, FeS₂@RBCs exhibited prolonged blood circulation, leading to improved tumor accumulation. FeS₂@RBCs showed TME-enhanced MRI after reacting with H₂O₂ in tumor regions for imaging-guided PTT. With an FDA-approved 1064 nm laser, FeS₂@RBCs achieved effective PTT, which significantly augmented the CDT effects for tumor synergetic therapy. The growth of tumors could be significantly inhibited by a clinically approved NIR-II laser. Reprinted with permission from Ref. [68]. Copyright 2020, Elsevier Inc.

Figure 5

Schematic illustration of the synthesis of FP NRs and their applications for US/PT-enhanced CDT and PTT in the NIR I/II window. PTMP stands for pentaerythritol tetrakis 3-mercaptopropionate and TOP stands for trioctylphosphine. Reprinted with permission from Ref. [69]. Copyright 2019, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 7

(A) A schematic illustrating the fabrication of acid-aggregated Fe-POM cluster. (B) Scheme showing Fe-POM for PTT-enhanced CDT in the NIR-II window. (C) UV-vis absorption spectra of o-phenylenediamine (OPD) changes by POM, POM + Fe²⁺ and Fe-POM. (D) GSH depletion under the reduction of different concentrations of Fe-POM (100, 200, 300, 400, 1000 μg mL⁻¹). DLS curves and TEM images of Fe-POM clusters at (E) pH 7.4 and (F) pH 6.4. (G) UV-vis spectra of Fe-POM dispersions at various concentrations. (H) UV-vis absorption spectra of OPD incubated with Fe-POM with or without laser irradiation. (I) Thermal images of mice injected with saline or Fe-POM (1060 nm laser, 1 W cm⁻²), tumor site with dot line circled. (J) In vivo PA images of tumor-bearing mice. (K) Tumor volumes in mice received three different groups. n = 4, mean ± SD. (**) < 0.01. (L) Representative photos of tumors after therapy (after 16 days of treatment). Reprinted with permission from Ref. [76]. Copyright 2020, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.