Abstract
Chemodynamic therapy (CDT) represents an emerging modality that treats cancer and other malignant diseases by using Fenton or Fenton-like catalysts to decompose hydrogen peroxide (H2O2) into toxic hydroxyl radicals (·OH). Despite its great promise, chemodynamic therapy is still limited by low endogenous H2O2 levels and lack of highly efficient nanocatalysts. In this study, we have developed multi-functional therapeutic nanocomposites GO–ZVI–GOx (GO = graphene oxide, ZVI = zero valence iron nanoparticles and GOx = glucose oxidase), where the GOx can catalyze the intracellular glucose and self-produce H2O2 for enhanced CDT therapy, and the GO is used as a template to avoid the aggregation of ZVI nanoparticles and also as an excellent photo-thermal converter for photothermal therapy under near-infrared (NIR) light. Our results show that this H2O2 self-generating nanoplatform can produce substantial amounts of reactive radicals under 808 nm NIR light due to the combinational effect of dual chemodynamic and photothermal therapy, which eventually leads to a significant decrease in cancer cell viability. It is believed that the methodology developed in this study enables conventional chemodynamic therapy to be efficiently improved, and holds great potential for overcoming challenges in many other H2O2-dependent cancer therapies.
Highlights
IntroductionChemodynamic therapy (CDT) refers to the cancer treatment that utilizes chemical agents to catalyze endogenous hydrogen peroxide (H2O2) into highly reactive oxygen species (ROS) via the Fenton or Fenton-like reactions in order to induce cell death.[1,2,3] Considering that the tumor microenvironment (TME) is characterized by mild acidity, Fenton-based CDT therapy is advantageous in its high tumor selectivity and speci city.[4,5] Part of the reason is that the Fenton reaction is signi cantly limited by the slightly basic microenvironment in the normal tissue region.[6,7] CDT therapy has emerged as a promising strategy for selective intervention in cancer and other malignant diseases.[8,9]
Since the $OH radicals produced by the Fenton reaction could react with benzoic acid (C6H5COOH) and form a uorescent product, the benzoic acid was used as a probe to detect the generation of $OH by graphene oxide (GO)–zero-valence iron (ZVI)–Glucose oxidase (GOx)
In order to solve the aggregation issue, the ZVI nanoparticles were in situ anchored on the GO surface, which process was mainly based on the redox reaction between the NaBH4 and Fe2+ ions adsorbed on GO surface
Summary
Chemodynamic therapy (CDT) refers to the cancer treatment that utilizes chemical agents to catalyze endogenous hydrogen peroxide (H2O2) into highly reactive oxygen species (ROS) via the Fenton or Fenton-like reactions in order to induce cell death.[1,2,3] Considering that the tumor microenvironment (TME) is characterized by mild acidity, Fenton-based CDT therapy is advantageous in its high tumor selectivity and speci city.[4,5] Part of the reason is that the Fenton reaction is signi cantly limited by the slightly basic microenvironment in the normal tissue region.[6,7] CDT therapy has emerged as a promising strategy for selective intervention in cancer and other malignant diseases.[8,9]. Wu et al reported that ZVI-based nanoparticles could selectively inhibit cancer cell but spare normal healthy ones,[17,18] which was attributed to the cancer-speci c cytotoxicity of the non-oxidized ZVI core in these nanoparticles.[19,20] Later, amorphous ZVI nanoparticles were reported and used for cancer therapy by triggering the local Fenton reaction in the tumor region.[2] In a more recent study, PVP (polyvinyl pyrrolidone) modi ed ZVI nanoparticles were demonstrated to have great potentials to serve as both the contrast agents for magnetic resonance imaging and the therapeutic reagents for synergetic cancer therapy.[21] Despite the great progress, the application of ZVI-based Fenton therapy is still limited by the low endogenous H2O2 level, insufficient generation of ROS and easy aggregation of ZVI nanoparticles. It is believed that the therapeutic nanoplatform developed in this work represents an efficient modality to resolve issues in the ZVIbased CDT treatment (e.g., insufficient endogenous H2O2 level and easy aggregation of ZVI nanoparticles) and hold great potential for improved cancer therapy
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