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Macrophages Loaded with Fe Nanoparticles for Enhanced Photothermal Ablation of Tumors.

ABSTRACT: Magnetic iron nanoparticle-based theranostics agents have attracted much attention due to their good magnetism and biocompatibility. However, efficiently enriching tumors with iron nanoparticles to enhance the treatment effect remains a pressing challenge. Herein, based on the targeting and high phagocytosis of macrophages, an Fe nanoparticle-loaded macrophage delivery system was designed and constructed to efficiently deliver iron nanoparticles to tumors. Hydrophilic Fe@Fe₃O₄ nanoparticles with a core-shell structure were synthesized by pyrolysis and ligand exchange strategy. Subsequently, they were loaded into macrophages (RAW264.7 cells) using a co-incubation method. After loading into RAW264.7, the photothermal performance of Fe@Fe₃O₄ nanoparticles were significantly enhanced. In addition, Fe@Fe₃O₄ nanoparticles loaded into the macrophage RAW264.7 (Fe@Fe₃O₄@RAW) exhibited a good T₂-weighted MRI contrast effect and clear tumor imaging in vivo due to the tumor targeting tendency of macrophages. More importantly, after being intravenously injected with Fe@Fe₃O₄@RAW and subjected to laser irradiation, the tumor growth was effectively inhibited, indicating that macrophage loading could enhance the tumor photothermal ablation ability of Fe@Fe₃O₄. The macrophage mediated delivery strategy for Fe@Fe₃O₄ nanoparticles was able to enhance the treatment effect, and has great potential in tumor theranostics.

SUBMITTER: Yu L

PROVIDER: S-EPMC9326737 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rationale: Chemodynamic therapy (CDT) based on the Fe(II)-mediated Fenton reaction is an emerging tumor treatment strategy. However, the catalytic efficiency in tumors is crucially limited by Fe(II). Herein, an endogenous hydrogen sulfide (H2S) accelerated Fe(III)/Fe(II) transformation and photothermal synergistically enhanced CDT strategy based on ellagic acid-Fe-bovine serum albumin (EA-Fe@BSA) nanoparticles (NPs) was developed for colon tumor inhibition. On the one hand, the Fe(III) with low catalytic activity in the EA-Fe@BSA NPs could be rapidly reduced to the highly active Fe(II) by the abundant H2S in colon cancer tissues. Thus, a rapid Fe(III)/Fe(II) conversion system was established, wherein highly active Fe(II) ions were continuously regenerated to improve the CDT efficiency. On the other hand, the photothermal effect of EA-Fe@BSA NPs also accelerated the production of hydroxyl radicals (•OH), thereby synergistically enhancing the CDT performance and improving the therapeutic efficacy. Methods: The endogenous H2S accelerated Fe(III)/Fe(II) conversion and PTT enhanced CDT were investigated by characterization of the Fe valence state and detection of •OH. T 1-weighted magnetic resonance imaging (MRI) was tested both in vitro and in vivo. The biocompatibility of NPs were examined via MTT assay, hemolysis analysis and routine blood measurements. The enhanced CDT was investigated in HCT116 colon cancer cells by Calcein-AM/PI staining and MTT assay, and tumor inhibition was demonstrated in HCT116 tumor bearing mice. Results: In this work, EA-Fe@BSA NPs were constructed as a CDT theranostic reagent. The H2S accelerated Fe(III)/Fe(II) conversion was confirmed, more degradation of MB and generation of •OH demonstrated the enhanced CDT in vitro. EA-Fe@BSA NPs exhibited good T 1-weighted MRI performance. More importantly, it displayed strong near-infrared (NIR) absorption and excellent photothermal efficiency, further promotes the production of •OH. Hence, the efficacy of CDT was enhanced, and the tumor growth was inhibited efficiently. Conclusion: All results demonstrate that this strategy based on endogenous H2S promoted Fe(III)/Fe(II) transformation together with PTT acceleration permits efficient Fenton-reaction- mediated CDT both in vitro and in vivo, which holds great potential for effective colon cancer theranostics.

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Macrophages Loaded with Fe Nanoparticles for Enhanced Photothermal Ablation of Tumors.

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