Manganese-based nanomaterials in diagnostics and chemodynamic therapy of cancers: new development

Abstract

In the realm of cancer treatment, traditional modalities like radiotherapy and chemotherapy have achieved certain advancements but continue to grapple with challenges including harm to healthy tissues, resistance to treatment, and adverse drug reactions. The swift progress in nanotechnology recently has opened avenues for investigating innovative approaches to cancer therapy. Especially, chemodynamic therapy (CDT) utilizing metal nanomaterials stands out as an effective cancer treatment choice owing to its minimal side effects and independence from external energy sources. Transition metals like manganese are capable of exerting anti-tumor effects through a Fenton-like mechanism, with their distinctive magnetic properties playing a crucial role as contrast agents in tumor diagnosis and treatment. Against this backdrop, this review emphasizes the recent five-year advancements in the application of manganese (Mn) metal ions within nanomaterials, particularly highlighting their unique capabilities in catalyzing CDT and enhancing MRI imaging. Initially, we delineate the biomedical properties of manganese, followed by an integrated discussion on the utilization of manganese-based nanomaterials in CDT alongside multimodal therapies, and delve into the application and future outlook of manganese-based nanomaterial-mediated MRI imaging techniques in cancer therapy. By this means, the objective is to furnish novel viewpoints and possibilities for the research and development in future cancer therapies.

Fig. 1. Manganese has the following four main functions: (1) physiological functions; (2) chemodynamic therapy and tumor microenvironment regulation; (3) immune defense; (4) magnetic resonance imaging.

Fig. 2. (a) Synthetic procedure for HMCP NCs. (b) The scheme of dual-mode ROS-therapeutic mechanism of HMCP NCs for combined cancer treatment. Copyright 2019, American Chemical Society.

Fig. 3. Scheme of the synthesis process and therapeutic mechanism of MPBC nanoplatform. Copyright 2022, Elsevier B. V.

Fig. 4. Scheme of the synthesis process and therapeutic mechanism of PP@Mn. Copyright CCBY, 2022, Informa UK Limited.

Fig. 5. Schematic diagram of multimodal therapy of manganese-based nanomaterials: (A) scheme of the synthesis process and therapeutic mechanism of SSMID NCs; copyright 2022, Elsevier B. V. (B) Schematic illustration of GOx-MnCaP-DOX applied for MRI-monitored cooperative cancer therapy; copyright 2019, American Chemical Society. (C) Scheme of the therapeutic mechanism of PBMO-GH; copyright 2021, Elsevier B. V. (D) Construction of PCP-Mn-DTA@GOx@1-MT and its immune stimulation capabilities. Copyright CCBY, 2022, Springer Nature.

Fig. 6. Pharmacokinetics and targeting effect and tumor suppression effects of intravenously injected NPs in vivo. (A) In vivo real-time bioluminescence imaging of UM tumor-bearing mice at different time points after administration of ICG-COP@MOF-PR; (B) ICG fluorescent intensities from ex vivo imaging of the major organs, and the tumors 24 h after injecting ICG-COP@MOF-PR; (C) T₁-weighted MRI after intravenous injection with ICG-COP@MOF-PR at predesigned time points; (D and E) the tumor growth curves and bioluminescence imaging showed UM growth with different treatments in vivo. Copyright CCBY, 2023, Springer Nature.

Fig. 7. In vivo multimodal imaging. (A) NIR-II FI of whole-body blood vessels of nude mice injected with PMR NAs solution via the tail vein. Fluorescence intensity profiles of the cross-sectional lines from (B) magnified abdominal vascular image and (C) magnified femoral vascular image. (D) NIR-II FI of B16F10 tumor-bearing mice injected with PMR NAs solution. (E) Mean fluorescence intensity in the tumor region. (F) PAI and (G) mean PA intensity of tumors from mice injected with PMR NAs solution. Scale bar: 3.5 mm. (H) MRI of cross-sections of mice and (I) mean MR signals of tumors after injection with PMR NAs. Copyright 2023, Elsevier Ltd.