Dataset Information

Fe₃O₄@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy.

ABSTRACT: Electrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe₃O₄@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe₃O₄@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H₂O₂ into ROS via Fenton reaction. In addition, Fe³⁺ ions released from Fe₃O₄@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.

SUBMITTER: Chen T

PROVIDER: S-EPMC8272323 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Fe3O4@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy.

Chen Tong T Chu Qiang Q Li Mengyang M Han Gaorong G Li Xiang X

Journal of nanobiotechnology 20210710 1

Electrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O< ...[more]

PMID: 34246260

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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.

Project description:Transition-metal ion copper(II) (Cu(II)) has drawn increasing attention as a small-molecular cancer theranostic agent. However, delivering a sufficient dosage of Cu(II) to the tumor site and integrating multiple imaging modalities to achieve precise and effective cancer theranostics remains a critical challenge. Herein, an emerging Cu(II)-based nanocomposite has been synthesized for targeted tumor computed tomography (CT)/magnetic resonance (MR) dual-mode imaging and chemodynamic therapy (CDT). Briefly, 2-picolinic acid (PA-COOH), polyethylene glycol (PEG)-linked folic acid (FA), and fluorescein isothiocyanate (FI) were sequentially conjugated with polyethylenimine (PEI.NH2) and then in situ fabrication of gold nanoparticles (Au NPs) occurred within the PEI.NH2 internal cavity. After acetylation of PEI.NH2 terminal amines and Cu(II) complexation, the Cu(II)-based nanocomposites FA-Au/Cu(II) PENPs with a mean diameter of 2.87 nm were generated. The synthesized FA-Au/Cu(II) PENPs showed favorable stability of colloidal dispersion, sustainable Cu(II) release properties in a pH-dependent manner, and Fenton-like catalytic activity specifically. With the FA-mediated targeting pathway, FA-Au/Cu(II) PENPs can specifically accumulate in cancer cells with high expression of FA receptors. Meanwhile, the complementary CT/MR dual-mode imaging in vitro and in vivo can be afforded by FA-Au/Cu(II) PENPs based on the excellent X-ray attenuation properties of Au NPs and the applicable r1 relaxivity (0.7378 mM-1s-1) of Cu(II). Notably, the Cu(II)-mediated CDT mechanism enables FA-Au/Cu(II) PENPs to elicit the generation of toxic hydroxyl radicals (·OH), depletion of glutathione (GSH), promotion of lipid peroxidation (LPO), and induction of cancer cell apoptosis in vitro, and further demonstrates remarkable anti-tumor efficacy in a xenograft tumor model. With the illustrated targeted theranostic capacity of FA-Au/Cu(II) PENPs towards tumors, this Cu(II)-based nanocomposite paradigm inspires the construction of advanced theranostic nanoplatforms incorporating alternative transition metal ions.

Dataset Information

Fe₃O₄@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy.

Publications

Fe<sub>3</sub>O<sub>4</sub>@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy.

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