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FeS@BSA Nanoclusters to Enable H2S-Amplified ROS-Based Therapy with MRI Guidance.

ABSTRACT: Therapeutic systems to induce reactive oxygen species (ROS) have received tremendous success in the research of tumor theranostics, but suffered daunting challenges in limited efficacy originating from low presence of reactants and reaction kinetics within cancer cells. Here, ferrous sulfide-embedded bovine serum albumin (FeS@BSA) nanoclusters, in an amorphous nature, are designed and synthesized via a self-assembly approach. In acidic conditions, the nanoclusters degrade and simultaneously release H2S gas and Fe2+ ions. The in vitro study using Huh7 cancer cells reveals that Fe2+ released from FeS@BSA nanoclusters induces the toxic hydroxyl radical (·OH) effectively via the Fenton reaction. More interestingly, H2S gas released intracellularly presents the specific suppression effect to catalase activity of cancer cells, resulting in the promoted presence of H2O2 that facilitates the Fenton reaction of Fe2+ and consequently promotes ROS induction within the cells remarkably. After intravenous administration, the nanoclusters accumulate in the tumors of mice via the enhanced permeability and retention effect and present strong magnetic resonance imaging (MRI) signals. The findings confirm this therapeutic system can enable superior anti-tumor performance with MRI guidance and negligible side effects. This study, therefore, offers an alternative gas-amplified ROS-based therapeutic platform for synergetic tumor treatment.

SUBMITTER: Xie C

PROVIDER: S-EPMC7141047 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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FeS@BSA Nanoclusters to Enable H<sub>2</sub>S-Amplified ROS-Based Therapy with MRI Guidance.

Xie Congkun C Cen Dong D Ren Zhaohui Z Wang Yifan Y Wu Yongjun Y Li Xiang X Han Gaorong G Cai Xiujun X

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200219 7

Therapeutic systems to induce reactive oxygen species (ROS) have received tremendous success in the research of tumor theranostics, but suffered daunting challenges in limited efficacy originating from low presence of reactants and reaction kinetics within cancer cells. Here, ferrous sulfide-embedded bovine serum albumin (FeS@BSA) nanoclusters, in an amorphous nature, are designed and synthesized via a self-assembly approach. In acidic conditions, the nanoclusters degrade and simultaneously rele ...[more]

PMID: 32274323

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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.

Dataset Information

FeS@BSA Nanoclusters to Enable H2S-Amplified ROS-Based Therapy with MRI Guidance.

Publications

FeS@BSA Nanoclusters to Enable H<sub>2</sub>S-Amplified ROS-Based Therapy with MRI Guidance.

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