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.

ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable H2S-amplified synergistic therapy

“…Meanwhile, H 2 S is induced intracellularly due to the degradation of ZnS in the acidic condition, which could regulate a number of key biological functions. Herein, despite its inhibition effect to Huh7 cancer cells, H 2 S also downregulates the CAT activity 45 , 46 , enabling the cutting of transformation from H 2 O 2 to O 2 and promoted hypoxia condition ( Figure S20 ). The toxicity of intracellular TPZ delivered by ZSZIT is agitated and activated by the severe hypoxia condition.…”

Photothermo‐Promoted Nanocatalysis Combined with H2S‐Mediated Respiration Inhibition for Efficient Cancer Therapy

“…[ 13 ] These gas molecules act as messengers in the process of specific binding with multivalent transition metals, endowing many physiological functions in human bodies. [ 14 ] For example, H 2 S gas is reported to suppress the expression to catalase activity of tumors cells, [ 15 ] or to facilitate the reduction of Fe 3+ to Fe 2+ , [ 16 ] thus promoting the efficiency of CDT in the presence of H 2 O 2 . H 2 S also could aggravate the hypoxia to activate hypoxia‐activated prodrug to enhance chemotherapy.…”

Intelligent Fe–Mn Layered Double Hydroxides Nanosheets Anchored with Upconversion Nanoparticles for Oxygen‐Elevated Synergetic Therapy and Bioimaging

“…The decomposed Fe 3+ could catalyze endogenous H 2 O 2 to O 2 for PDT of UCSP while simultaneously being reduced to Fe 2+ , and Fe 2+ will then continue to generate •OH by undergoing a Fenton reaction with H 2 O 2 . [64,65] Mn 2+/3+ could react with H 2 O 2 to form Mn 3+/4+ and •OH, [66,67] the above reactions together constitute the CDT. In this way, the high yield of generated 1 O 2 by UCSP and •OH could cause efficient cell apoptosis and necrosis.…”