Efficiency Of Fenton Reaction Research Articles

Dendrimer/metal-phenolic nanocomplexes encapsulating CuO2 for targeted magnetic resonance imaging and enhanced ferroptosis/cuproptosis/chemodynamic therapy by regulating the tumor microenvironment

The combination of ferroptosis, cuproptosis, and chemodynamic therapy (CDT) would be a potential strategy for tumor diagnosis and enhanced treatment. However, the therapeutic effect was severely limited by the lack of specific delivery of catalytic ions and the low Fenton reaction efficiency in tumor microenvironment (TME) with excess glutathione, limited acidity and insufficient endogenous hydrogen peroxide. In this work, p-carboxybenzenesulfonamide (BS), a carbonic anhydrase IX (CA IX) inhibitor, was modified on the surface of generation-5 poly(amidoamine) dendrimer to load copper peroxide nanoparticles, which were complexed with iron (Fe)-tannic acid (TF) networks for targeted magnetic resonance (MR) imaging and enhanced ferroptosis/cuproptosis/CDT by regulating TME. The formed CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm could be specifically accumulated at tumor site and effectively internalized by metastatic 4T1 cells via the specific interaction between BS and CA IX over-expressed on tumor cells. Meanwhile, the inhibition of CA IX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity in TME. Moreover, the reduction of Fe3+/Cu2+ by intracellular glutathione (GSH) could further amplify ROS generation and enhance CDT efficacy, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy. In vivo experimental results demonstrated that CuO2@G5-BS/TF could provide better tumor MR imaging, effectively inhibit the growth and metastasis of 4T1 breast tumors, and be metabolized without significant systemic toxicity. Thus, CuO2@G5-BS/TF nanocomplexes provided a new approach for targeted MR imaging and enhanced ferroptosis/cuproptosis/CDT of triple-negative breast cancer. Statement of significanceTaking the advantage of dendrimer and metal-phenolic system, stable CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm were synthesized to efficiently load Fe3+ and CuO2 nanoparticles for TNBC treatment and MR imaging. CuO2@G5-BS/TF nanocomplexes could target tumor cells overexpressing CAIX via the specific binding with BS, and the inhibition of CAIX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity. The reduction of Fe3+/Cu2+ by intracellular GSH could further amplify ·OH generation, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy by enhanced ferroptosis/cuproptosis/CDT via tumor microenvironment regulation.

Enhanced catalytic activity of Fe3O4-carbon dots complex in the Fenton reaction for enhanced immunotherapeutic and oxygenation effects

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.

Comprehensive study of Fenton reaction efficiency on textile wastewater treatment from dye solution to real effluent with emphasis on Fukui function analysis

This study investigated the continuous degradation monitoring of three reactive dyes, reactive yellow 176 (RY), reactive Blue 4 (RB) and reactive red 293 (RR), both in separate solutions and in a mixture, along with their corresponding dye bath and industrial dyeing effluent, using Fenton reaction. A kinetic study was conducted to compare the degradation efficiency of the studied solutions. This work provides important yield of dye degradation, where the results showed that RB, RY, and RR had 96.64 %, 92.47 %, and 73.27 % color removal, respectively, within a two-hour reaction time. The pseudo-second-order model fit well to describe the degradation of RR and RY, while the zero-pseudo-order model provided a better fit for RB. The dye mixture exhibited 57 % color removal, whereas the dyeing bath and real effluent showed 41 % and 36 % removal, respectively, over a two-hour reaction time. Moreover, significant reductions in chemical oxygen demand (COD) and biological oxygen demand over 5 days (BOD5) were observed, with the real effluent demonstrating a 73.91 % COD reduction and an 86.66 % reduction in BOD5. The COD and BOD5 reductions for the dye bath were 67.53 % and 95 %, respectively. Additionally, COD and BOD5 reductions of 72.96 % and 96.66 %, respectively, were observed for the dye bath. DFT calculations were employed to elucidate the regioselectivity of radical oxidation of the three reactive dyes by Fenton's reagent, providing insights into global and local reactivity descriptors. Toxicity studies further underscored the efficacy of the Fenton reaction in wastewater treatment. Additionally, UV–visible spectral analysis before and after 12 h of Fenton reaction revealed total discolouration and a reduction in UV and visible peaks across all reactions, indicating comprehensive dye degradation and reduction.

Oxygen vacancy boosting Fenton reaction in bone scaffold towards fighting bacterial infection

Bacterial infection is a major issue after artificial bone transplantation due to the absence of antibacterial function of bone scaffold, which seriously causes the transplant failure and even amputation in severe cases. In this study, oxygen vacancy (OV) defects Fe-doped TiO2 (OV-FeTiO2) nanoparticles were synthesized by nano TiO2 and Fe3O4 via high-energy ball milling, which was then incorporated into polycaprolactone/polyglycolic acid (PCLGA) biodegradable polymer matrix to construct composite bone scaffold with good antibacterial activities by selective laser sintering. The results indicated that OV defects were introduced into the core/shell-structured OV-FeTiO2 nanoparticles through multiple welding and breaking during the high-energy ball milling, which facilitated the adsorption of hydrogen peroxide (H2O2) in the bacterial infection microenvironment at the bone transplant site. The accumulated H2O2 could amplify the Fenton reaction efficiency to induce more hydroxyl radicals (·OH), thereby resulting in more bacterial deaths through ·OH-mediated oxidative damage. This antibacterial strategy had more effective broad-spectrum antibacterial properties against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In addition, the PCLGA/OV-FeTiO2 scaffold possessed mechanical properties that match those of human cancellous bone and good biocompatibility including cell attachment, proliferation and osteogenic differentiation.

Comprehensively Optimizing Fenton Reaction Factors for Antitumor Chemodynamic Therapy by Charge-Reversal Theranostics.

Chemodynamic therapy (CDT) is a highly tumor-specific treatment, while its efficacy is compromised by the intratumoral Fenton reaction efficiency, which is determined by the following reaction factors, including the availability of Fenton ions (e.g., Fe2+), the amount of H2O2, and the degree of acidity. Synchronous optimization of these factors is a big challenge for efficient CDT. Herein, a strategy of comprehensively optimizing Fenton reaction factors was developed for traceable multistage augmented CDT by charge-reversal theranostics. The customized pH-responsive poly(ethylene)glycol-poly(β-amino esters) (PEG-PAE) micelle (PM) was prepared as the carrier. Glucose oxidase (GOx), Fe2+, and pH-responsive second near-infrared (NIR-II) LET-1052 probe were coloaded by PM to obtain the final theranostics. The activity of metastable Fe2+ remained by the unsaturated coordination with PEG-PAE. Then tumor accumulation and exposure of Fe2+ were achieved by charge-reversal cationization of PEG-PAE, which was further enhanced by a GOx catalysis-triggered pH decrease. Together with the abundant H2O2 generation and pH decrease through GOx catalysis, the limiting factors of the Fenton reaction were comprehensively optimized, achieving the enhanced CDT both in vitro and in vivo. These findings provide a strategy for comprehensively optimizing intratumoral Fenton reaction factors to overcome the intrinsic drawbacks of current CDT.

UCNPs-based nanoreactors with ultraviolet radiation-induced effect for enhanced ferroptosis therapy of tumor

The limitations of light source limit the clinical application of optical therapy technology. How to improve the application efficiency of radiant light has become the focus of researchers. Here, we synthesize a kind of UCNPs@PVP-GOx-PpIX-Fe3+ (UPGPF) nanoreactors with rare earth upconversion nanoparticles (UCNPs) as the substrate for the enhancement of ferroptosis effect by the synergistic starvation/photodynamic therapies. Firstly, glucose oxidase (GOx) and Fe3+ loaded in UPGPF nanoreactors are used to directly face the problems of insufficient H2O2 level in tumor tissue and low Fenton reaction efficiency. Further, UCNPs can absorb NIR light at 980 nm and convert low-energy photons into high-energy photons, thereby cleverly generating ultraviolet (UV) radiation induction in vivo, which can produce a synergistic effect of enhancing iron death. The in vivo experimental results of breast cancer model mice show that the UPGPF nanoreactors have significant anticancer effect and good biosafety. With the help of the optical conversion characteristics of UCNPs, this kind of treatment idea of building a UV radiation-induced microplatform in the tumor microenvironment, which leads to the synergistic enhancement of iron death effect, provides a promising innovative design strategy for tumor research.

The effect of FeS on the fate of Cr(VI) in the presence of organic matters under dynamic anoxic/oxic conditions.

The reduction of Cr(VI) by FeS under anoxic conditions has been studied extensively. However, when the redox environments alternate from anoxic to oxic, the effect of FeS on the fate of Cr(VI) in the presence of organic matters still remains unknown. Therefore, this study investigated the effect of FeS coupled with humic acids (HA) and alga on the transformation of Cr(VI) under dynamic anoxic/oxic conditions. HA could promote the reduction of Cr(VI) from 86.6% to 100% under anoxic conditions due to the enhancement of the dissolution and dispersibility of FeS particles by HA. However, the strong complexing and oxidizing properties of alga inhibited the reduction of FeS. Reactive oxygen species (ROS) generated from FeS oxidation under oxic conditions could oxidize 3.80μM of Cr(III) to aqueous Cr(VI) at pH 5.0, while aqueous Cr(VI) reached to 4.83μM in the presence of HA, which was ascribed to the increasing amount of free radicals. In addition, acidic conditions and excess FeS would increase strong reducing Fe(II) and S(-II) species, and improve the efficiency of Fenton reaction. The findings provided new insights into the fate of Cr(VI) in aquatic systems containing FeS and organic matters under dynamic anoxic/oxic conditions.

Targeted Magnetic Resonance Imaging/Near‐Infrared Dual‐Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

AbstractAccurate identification and visualization of peritoneal metastases (PM) are clinically essential to improving the prognosis for gastric cancer. However, owing to the multifocal spread of peritoneal metastasis nodules, small size, and close contact with adjacent organs, identifying and completely removing them during surgery is extremely challenging, resulting in cancer treatment failure and recurrence. This study develops a T1‐weighted magnetic resonance imaging (MRI) contrast agent (FeGdNP)‐loaded indocyanine green/glucose oxidase (ICG/GOx) with conjugation of an RGD dimer (RGD2) and acid‐labile polymer mPEG (FeGdNP‐ICG/GOx‐RGD2‐mPEG). Compared with commercial Magnevist, the proposed FeGdNP‐ICG/GOx‐RGD2‐mPEG shows a two to three‐fold higher tumor ΔSNR in MRI of peritoneal metastasis and subcutaneous animal models. Compared with free ICG, the increased fluorescent signal of FeGdNP‐ICG/GOx‐RGD2‐mPEG allows for the detection of tiny tumor metastatic nodules (<3 mm), and the removal of the peritoneum transplanted tumors. Abundant gluconic acid and H2O2 are generated during the GOx‐mediated glucose depletion process in cancer cells, thereby enhancing Fenton reaction efficiency. Accumulated toxic ·OH can damage the mitochondrial function and induce the release of mitochondrial reactive oxygen species, which activates the ferroptosis pathway. The data indicate the potential of the nanoparticles for MRI preoperative diagnosis, intraoperative fluorescence‐guided navigation, and ferroptosis tumor therapy.

A novel dual MoS2/FeGA quantum dots endowed injectable hydrogel for efficient photothermal and boosting chemodynamic therapy.

Due to its responsiveness to the tumour microenvironment (TME), chemodynamic therapy (CDT) based on the Fenton reaction to produce cytotoxic reactive oxygen species (ROS) to destroy tumor has drawn more interest. However, the Fenton’s reaction potential for therapeutic use is constrained by its modest efficacy. Here, we develop a novel injectable hydrogel system (FMH) on the basis of FeGA/MoS2 dual quantum dots (QDs), which uses near-infrared (NIR) laser in order to trigger the synergistic catalysis and photothermal effect of FeGA/MoS2 for improving the efficiency of the Fenton reaction. Mo4+ in MoS2 QDs can accelerate the conversion of Fe3+ to Fe2+, thereby promoting the efficiency of Fenton reaction, and benefiting from the synergistically enhanced CDT/PTT, FMH combined with NIR has achieved good anti-tumour effects in vitro and in vivo experiments. Furthermore, the quantum dots are easily metabolized after treatment because of their ultrasmall size, without causing any side effects. This is the first report to study the co-catalytic effect of MoS2 and Fe3+ at the quantum dot level, as well as obtain a good PTT/CDT synergy, which have implications for future anticancer research.

Defective Cu2-xSe crystals for ultrasound-enhanced CDT of tumor therapy

Chemodynamic therapy (CDT) uses endogenous H2O2 to produce toxic reactive oxygen species (ROS) for killing cancer cells, but it is hindered by low efficiency of Fenton reaction in tumor microenvironment (TME). Hereby, we have developed Cu2-xSe-PEG for ultrasound-enhanced CDT of tumor. Due to the inherent copper deficiency, the Cu2-xSe crystals generated abundant reactive oxygen (ROS) to induce tumor cells death under ultrasound (US) irradiation. Meanwhile, the ultrasound enhanced the Fenton reaction efficiency and thereby promoted CDT effect. Thus, this study opens an example of Cu-defective compound for noninvasive ultrasound-enhanced CDT for tumor.

Multifunctional nanosystems sequentially regulating intratumor Fenton chemistry by remodeling the tumor microenvironment to reinforce chemodynamic therapy.

The particularity of the tumor microenvironment (TME) significantly limits the efficiency of chemodynamic therapy (CDT). Although various measures have been taken to improve the efficiency of CDT, how to organically integrate them into one nanosystem to achieve efficient synergy for CDT according to predetermined procedures is still an urgent problem to be solved. This work reported a multifunctional nanosystem, TPI@PPCAI, which comprised the inner triphenylphosphine modified D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS-PPh3) micelles loading iron-oxide nanoparticles (IONs), and the outer poly (dopamine-co-protocatechuic acid) (PDA-PA, PP) coating modified with carbonic anhydrase IX inhibitor (CAI). TPI@PPCAI remodeled TME by sequential function adjustment to make it suitable for the efficient Fenton reactions: CAI first inhibited the overexpressed CA IX to result in intracellular acidification, which combined with near-infrared light (NIR) irradiation to accelerate the PP coating degradation, thereby promoting the exposure and disintegration of the inner micellar structure to release TPGS-PPh3 and IONs. The TPGS-PPh3 further elevated the intracellular ROS basal level by targeting and interfering with the mitochondrial function. Therefore, the TME was transformed into an acidic microenvironment with high ROS levels, which vigorously promoted the Fenton reaction mediated by IONs with the aid of photothermal effect induced by PP coating via NIR irradiation, ultimately earning high-efficiency CDT on xenograft MDA-MB-231 tumor-bearing mice. This study improved the efficiency of Fenton reaction in biological systems through the practical design of nanostructures and provided a novel thought for ROS-mediated therapy.

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy.

Ferroptosis therapy by catalyzing the Fenton reaction has emerged as a promising tumor elimination strategy for lung adenocarcinoma (ADC). However, the unsatisfactory Fenton reaction efficiency, strong intracellular antioxidant system, and insufficient lung drug accumulation limits the ferroptosis therapeutic effect. To address these issues, an inhalable nanoreactor was proposed by spontaneously adsorbing biomimetic protein corona (PC) composed of matrix metalloproteinase 2 responsive gelatin and glutamate (Glu) on the surface of cationic nanostructured lipid carriers (NLC) core loaded with ferrocene (Fc) and fluvastatin. The prepared Fc-NLC(F)@PC could be nebulized into lung lesions with 2.6 times higher drug accumulation and boost lipid peroxide production by 3.2 times to enhance ferroptosis therapy. Mechanically, fluvastatin was proved to inhibit monocarboxylic acid transporter 4 mediated lactate efflux, inducing tumor acidosis to boost Fc-catalyzing reactive oxygen species production, while the extracellular elevating Glu concentration was found to inhibit xCT (system Xc-) functions and further collapse the tumor antioxidant system by glutathione synthesis suppression. Mitochondrial dysfunction and cell membrane damage were involved in the nanoreactor-driven ferroptotic cell death process. The enhanced antitumor effects by combination of tumor acidosis and antioxidant system collapse were confirmed in an orthotopic lung ADC tumor model. Overall, the proposed nanoreactor highlights the pulmonary delivery approach for local lung ADC treatment and underscores the great potential of ferroptosis therapy.

Novel FeF2/Fe1–xS Nanoreactor‐Mediated Mitochondrial Dysfunction via Oxidative Stress and Fluoride Ions Overloaded for Synergistic Chemodynamic Therapy and Photothermal Therapy

AbstractSelecting subcellular organelles as therapeutic targets have drawn great interest for cancer treatment. Herein, novel nanotheranostic agents FeF2/Fe1–xS nanorods modified by polyethylene glycol (FFSNRs‐PEG) are first synthesized for tumor microenvironments (TME) responsive magnetic resonance imaging (MRI) guided synergetic cancer therapy focused on the mitochondria. In TME, the Fe2+ and F− ions released from FFSNRs‐PEG can make mitochondrial damage via the production of toxic ·OH through Fenton reaction and activation of caspase‐3, resulting in apoptosis and cell death. Taking advantage of the strong absorption of FFSNRs‐PEG in the second biowindow (1000–1700 nm), the photothermal effect boosts the efficiency of Fenton reaction to achieve synergetic chemodynamic therapy and photothermal therapy under near‐infrared light (1064 nm) irradiation. In addition, benefiting from the self‐oxidation effect, the FFSNRs‐PEG can serve as a novel TME‐responsive contrast agent for T2‐weighted MRI. Overall, this work highlights an innovative “weapon” to realize TME‐responsive tumor diagnosis and synergetic therapies focused on the mitochondria.

An active-passive strategy for enhanced synergistic photothermal-ferroptosis therapy in the NIR-I/II biowindows.

Ferroptosis therapy (FT) is an attractive strategy to selectively damage cancer cells through lipid peroxide (LPO) over-accumulation. However, this therapy suffers from poor therapeutic efficacy due to the limited Fenton reaction efficiency and the evolved intrinsic resistance mechanism in the tumor microenvironment (TME). The exploitation of novel ferroptosis inducers is of significance for improving the efficacy of FT. Here, we develop a plate-like Bi2Se3-Fe3O4/Au (BFA) theranostic nanoplatform, which can increase the Fenton reaction rate to enhance FT in an active-passive way. In detail, benefiting from the internal synergistic effect of Fe3O4 NPs and Au NPs and external NIR-mediated hyperthermia, the BFA NPs can boost hydroxyl radical (˙OH) generation to enhance intracellular oxidative stress and further induce ferroptosis by inactivating glutathione peroxidase 4 (GPX4). Furthermore, the BFA NPs show high photothermal conversion efficiency in both the NIR-I and NIR-II windows (66.2% at 808 nm and 58.2% at 1064 nm, respectively); therefore, as a photothermal agent (PTA), they can also ablate cancer cells directly by NIR-triggered photothermal therapy (PTT). Meanwhile, BFA NPs could be used as an efficient diagnostic agent for photoacoustic (PA)/magnetic resonance (MR)/X-ray imaging to guide the synergistic therapy of photothermal-ferroptosis. Therefore, BFA NP-mediated enhanced photothermal-ferroptosis therapy represents a promising strategy for the application of nanomaterials in tumor therapy.

Construction of Fe3O4@FeS2@C@MoS2 Z-scheme heterojunction with sandwich-like structure: Enhanced catalytic performance in photo-Fenton reaction and mechanism insight

Herein, the sandwich-like Fe3O4@FeS2@C@MoS2 composite was prepared via coating MoS2 shell on the surface of core/shell Fe3O4@C composite. During the coating process, Fe3O4 was partly sulfurized to FeS2, whose energy band was well-matched with that of MoS2 for a Z-scheme heterojunction. The residual Fe3O4 ensured the rapid separation of heterojunction by magnet. In photo-Fenton reaction, 81.5% of tetracycline was degraded within 40 min, which was higher than the sum of degradation efficiency of Fenton reaction and photocatalytic reaction. 93.6% of the degradation efficiency in the 1st cycle was still maintained after 5 cycles. In mechanism study, the sources of •OH, •O2-, 1O2 and h+ were carefully traced, and the contributions of these radicals followed the order: •OHsurf>•O2->1O2>h+>•OHfree. An inner electric field was built at the interface by analyzing the energy band and work functions, which driven the charge carriers transfer followed a Z-scheme path. The findings in this manuscript were beneficial for designing catalysts with high photo-Fenton activity.

Synthesis of taurine-Cu3(PO4)2 hybrid nanoflower and their peroxidase-mimic and antimicrobial properties

Herein, we report the synthesis of taurine incorporated (sulfur containing organic molecule derived from methionine and cysteine) hybrid nanoflowers (thNFs) with an intrinsic peroxidase-mimic and antimicrobial activities in the presence of H2O2. Formation of thNFs using non-enzyme molecules was for the first time and systematically studied as a function of the taurine concentration, types of metal ions (Cu2+, Fe2+ and Fe3+) and pH values of reaction solution. The peroxidase like activities of thNFs rely on Fenton-like reaction against guaiacol used as a model substrate. The efficiency of Fenton reaction can be attributed to porous structure and presence of ions of transition elements in the thNFs. The thNFs were further characterized using FTIR, XRD, SEM and EDX. The thNFs also showed remarkable antimicrobial properties against S. aureus, E. coli, B. cereus and C. albicans. We claim that nonprotein-based NFs can be considered as new generation nano-biocatalysts as an alternative to enzymes and can be used in various medicinal, biochemical, immunological, biotechnological, and industrial applications.

Achieving NIR Light-Mediated Tumor-Specific Fenton Reaction-Assisted Oncotherapy by Using Magnetic Nanoclusters.

As an emerging strategy for oncotherapy, Fenton chemistry can efficiently improve the conversion from endogenous H2O2 into highly toxic ·OH in the whole high-performance therapeutic process. Although promising, the efficiency of Fenton reaction in tumor regions is highly limited by the inefficient delivery of Fenton reagents and the restrictive conditions of tumor microenvironment. One promising strategy against the above limitations is to specifically increase the temperature around the tumor regions. In this study, a novel NIR light-mediated tumor-specific nanoplatform based on magnetic iron oxide nanoclusters (MNCs) was rationally designed and well developed for photothermally enhanced Fenton reaction-assisted oncotherapy. MNCs could accumulate into the tumor regions with the help of an external magnet field to enable T2-weighted magnetic resonance (MR) imaging of tumors and MR imaging-guided combined antitumor therapy. Our well-prepared MNCs also revealed excellent photothermal effect upon a NIR light irradiation, promising their further important role as a photothermal therapy (PTT) agent. More importantly, heat induced by the PTT of MNCs could accelerate the release of Fe from MNCs and enhance the efficiency of Fenton reaction under H2O2-enriched acidic tumor microenvironment. Results based on long-term toxicity investigations demonstrated the overall safety of MNCs after intravenous injection. This work therefore introduced a novel nanoplatform based on MNCs that exerted a great antitumor effect via photothermally enhanced tumor-specific Fenton chemistry.

Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic-Synergized Multimodal Therapy.

Chemodynamic therapy (CDT) uses the tumor microenvironment-assisted intratumoral Fenton reaction for generating highly toxic hydroxyl free radicals (•OH) to achieve selective tumor treatment. However, the limited intratumoral Fenton reaction efficiency restricts the therapeutic efficacy of CDT. Recent years have witnessed the impressive development of various strategies to increase the efficiency of intratumoral Fenton reaction. The introduction of these reinforcement strategies can dramatically improve the treatment efficiency of CDT and further promote the development of enhanced CDT (ECDT)-based multimodal anticancer treatments. In this review, the authors systematically introduce these reinforcement strategies, from their basic working principles, reinforcement mechanisms to their representative clinical applications. Then, ECDT-based multimodal anticancer therapy is discussed, including how to integrate these emerging Fenton reinforcement strategies for accelerating the development of multimodal anticancer therapy, as well as the synergistic mechanisms of ECDT and other treatment methods. Eventually, future direction and challenges of ECDT and ECDT-based multimodal synergistic therapies are elaborated, highlighting the key scientific problems and unsolved technical bottlenecks to facilitate clinical translation.

Photothermal nanozyme-ignited Fenton reaction-independent ferroptosis for breast cancer therapy

Ferroptosis is a type of programmed cell death caused by the iron-dependent lipid hydroperoxide pathway and has attracted significant interest. However, Fenton reaction-dependent ferroptosis has shown unsatisfactory therapeutic effects in tumor therapy, mainly due to inadequate reaction conditions in the tumor microenvironment. Here, we report a new strategy for Fenton-independent pathway by employing photothermal nanozyme to overcome limitations of the low efficiency of Fenton reaction. Specifically, we used iron redox pair (Fe2+/Fe3+)-containing hollow mesoporous Prussian blue (HMPB) nanocubes as the iron sources to fabricate iron-loaded liposome (HMPB@Lip). HMPB@Lip not only exerts the photothermal therapy, but also functions as nanozyme catalyzing lipid peroxidation for ferroptosis therapy. Importantly, Fenton reaction-independent ferroptosis triggered by photothermal nanozyme achieved effective tumor ablation. Therefore, HMPB@Lip can be used as a potential multifunctional nanozyme for effective Fenton reaction-independent ferroptosis therapy.

Titania/iron oxide nanoplatform operates as hydrogen peroxide enriched vector for amplification of fenton catalytic efficiency in cancer theranostics

The •OH induced apoptosis is a promising strategy for tumor treatment. Many current •OH generating systems are highly dependent on H2O2 in tumor microenvironment (TME). However, the H2O2 level in the TME is not high enough to produce sufficient •OH. Herein, we develop a biomimetic nano-catalyst based on TiO2/Fe3O4 platform (designed as “FTP”) to initiate a cascade of biochemical reactions to produce •OH in TME. In this platform, the modified TiO2 acting as H2O2 adsorber can promote the concentration of H2O2 around and significantly amplify Fenton reaction efficiency of Fe3O4 to induce more cell apoptosis through •OH mediated mechanism, thereby resulting in remarkable inhibition of tumor growth. The as-synthesized FTP, with diameter of 7.20 ± 1.80 nm, could efficiently accumulate in tumor via the enhanced permeability and retention (EPR) effect and act as negative T2-weighted MRI contrast agent. The results showed that the FTP could induce a significantly higher cytotoxicity profile than naked Fe3O4 nanoparticles. More specifically, the FTP exhibited significant therapeutic performance of tumors than naked Fe3O4, TiO2, and control groups.