Recent advances in ferrocene-based nanomedicines for enhanced chemodynamic therapy

Abstract

Malignant tumors have been a serious threat to human health with their increasing incidence. Difficulties with conventional treatments are toxicity, drug resistance, and recurrence. For this reason, non-invasive treatment modalities such as photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), and others have received much attention. Among them, Ferrocene (Fc)-based nanomedicines for enhanced Chemodynamic Therapy (ECDT) is a new therapeutic strategy based on the Fenton reaction. Based on ferrocene's good biocompatibility, potentiation in medicinal chemistry, and good stability of divalent iron ions, scientists are increasingly using it as a Fenton's iron donor for tumor therapy. Such ferrocene-based ECDT nanoplatforms have shown remarkable promise for clinical applications and have significantly increased the efficacy of CDT treatment. Ferrocene-based nanomedicines exhibit exceptional consistency owing to their low toxicity, high stability, enhanced bioavailability, and a multitude of advantages over conventional approaches to cancer treatment. As a consequence, a number of tactics have been investigated in recent years to raise the effectiveness of ferrocene-based ECDT. In this review, we detail the different forms and strategies used to enhance Ferrocene-based ECDT efficiency.

Keywords: Enhanced Chemodynamic therapy (ECDT); Ferrocene; Nanomedicine; Synergistic therapy.

Scheme 1

The schematic illustration for the type of Ferrocene-based nanomedicines and applications of enhanced CDT.

Figure 1

(A) Synthesis and therapeutic mechanisms of CaO₂/Co-Ferrocene NPs. Reproduced with permission from ref . Copyright 2021, Springer. (B) Working principle and preparation of CaO₂/Cu-ferrocene NPs. Reproduced with permission from ref . Copyright 2021, Wily. (C) Synthesis route and workflow of Fc-CD-AuNCs. Reproduced with permission from ref . Copyright 2024, Wily.

Figure 2

(A) Working principle and preparation of CPNPs. Reproduced with permission from ref . Copyright 2021, ACS. (B) Synthesis and therapeutic mechanisms of Zr-Fc MOF. Reproduced with permission from ref . Copyright 2020, ACS. (C) Synthesis route and workflow of RSL3@COF-Fc. Reproduced with permission from ref . Copyright 2021, Wily. (D) Schematic diagram of therapeutic mechanisms of TADI-COF-Fc. Reproduced with permission from ref . Copyright 2023, Wiley-VCH.

Figure 3

(A) Synthesis and therapeutic mechanisms of GOx@T-NPs. Reproduced with permission from ref . Copyright 2021, ACS. (B) Working principle and preparation of GOD/TPZ@PFc. Reproduced with permission from ref . Copyright 2021, Elsevier. (C) Synthesis route and workflow of PFW-DOX/GOD. Reproduced with permission from ref . Copyright 2022, Elsevier. (D) Schematic diagram of therapeutic mechanisms of Co-Fc NMOF. Reproduced with permission from ref . Copyright 2020, Wiley-VCH.

Figure 4

(A) Synthesis process and therapeutic mechanisms of mPEG-b-PPLGFc@Dox. (B) The dox release rate of mPEG-b-PPLGFc@Dox and variations in coloring of the liquids after 72 hours. (C) The degree of ROS in various treatments (D) LPO and GSH quantities in various treatment conditions. Reproduced with permission from ref . Copyright 2023, Wiley-VCH. (E) Working principle and preparation of cis-CD-Fc. (F) Representative TEM images of cis-CD-Fc. (G) The tumor volume, survival, and final tumor weight curves. (H) photographs of the dissected tumors and H&E, TUNEL staining image. Reproduced with permission from ref . Copyright 2021, Wiley-VCH.

Figure 5

(A) Enhanced the Fc-based complex and its anti-tumor mechanism through schematic representation. Reproduced with permission from ref . Copyright 2022, RSC. (B) Schematic diagram of therapeutic mechanisms of Fc-HP/HD/GOx. Reproduced with permission from ref . Copyright 2022, Elsevier. (C) Schematic description of the fabrication and anticancer mechanism of Lac-FcMOF. Reproduced with permission from ref . Copyright 2024, Wily.

Figure 6

(A) Synthesis process and therapeutic mechanisms of Ce6-CD / Fc-pep-PEG. (B) CLSM of 4T1 MSCs incubated with Ce6-CD/Fc-pep-PEG-FITC (4 h) and fluorescence semi-quantification. (C) Micro-CT images and H&E staining images of the metastatic tumor-bearing tibias. Reproduced with permission from ref . Copyright 2021, Wiley-VCH. (D) Synthesis route and workflow of PCF-PDP NPs. (E) Cell viability at various treatments. (F) FL of mice injected with PCF-PDP NPs. (G) Evaluation of treatment effects of PCF-PDP NPs Reproduced with permission from ref . Copyright 2023, Wiley-VCH.

Figure 7

(A) Synthesis process and therapeutic mechanisms of BP^nbs-Fc. (B) GPC date for the micellar dispersion, TEM images of the dispersion of BP^nbs-Fc, and Time-dependent changes of BP^nbs-Fc with different treatments. (C) Reaction scheme of iron ions produced from BP^nbs-Fc, time-dependent development of absorbance intensity of BP^nbs-Fc at different pH values, and BPnbs-Fc iron ions in vitro under various treatments. (D) NIR FL image after intravenous injection of BP^nbs-Fc and BP^Bn-Fc. Reproduced with permission , copyright 2023, Wiley-VCH. (E) Activation mechanism of IR-FEP-RGD-S-S-S-Fc. (F) CLSM images of Intracellular H₂S and COX IV. (G) NIR-II fluorescence images of IR-FEP-RGD-S-S-S-Fc. Reproduced with permission , copyright 2023, Wiley-VCH.

Figure 8

(A) Synthesis process and therapeutic mechanisms of RENC@IFS-Fc@PC. (B) Flow chart of PEG cleavage and pH response of IFS-Fc. (C) NIR-II FL imaging and peripheral tissues. (D) NIR-II FL imaging of RENC@IFS-Fc@PC and RENC@IFS-Fc@nPC. Reproduced with permission , copyright 2023, ACS. (E) Synthesis route and workflow of PpIX@M_Fc (F) LPO under different experimental conditions. Reproduced with permission , copyright 2022, Wiley-VCH.

Figure 9

(A) Synthesis of pHEA-b-pFcAam and pHEA-b-pIMDQ and CDT destroys tumor cells and further induces ICD and enhances immune response. (B-D) Schematic representation and timing of important proteins or substances expressed or secreted by stimulated T cells. Reproduced with permission , copyright 2023, Elsevier. (E) Synthesis and therapeutic modalities of IR-FE-Fc@DSPE-S-S-PEG. (F) Tumor in vivo imaging and immune changes. Reproduced with permission , copyright 2023, Elsevier.

Figure 10

(A) Synthesis and therapeutic mechanisms of Arg/Fc@GOx/HA. Reproduced with permission . Copyright 2023, Wiley-VCH. (B) Synthesis and therapeutic mechanisms of FTEB-TBFc. Reproduced with permission , copyright 2023, ACS.