Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC.

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.

Facile Synthesis of Self-Targeted Zn2+ -Gallic acid Nanoflowers for Specific Adhesion and Elimination of Gram-Positive Bacteria.

Transition metal ions are served as disinfectant thousand years ago. However, the in vivo antibacterial application of metal ions is strongly restricted due to its high affinity with proteins and lack of appropriate bacterial targeting method. Herein, for the first time, Zn2+ -gallic acid nanoflowers (ZGNFs) are synthesized by a facile one-pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution while can be easily decomposed in acidic environments. Besides, ZGNFs can specifically adhere onto Gram-positive bacteria, which is mediated by the interaction of quinone from ZGNFs and amino groups from teichoic acid of Gram-positive bacteria. ZGNFs exhibit high bactericidal effect toward various Gram-positive bacteria in multiple environments, which can be ascribed to the in situ Zn2+ release on bacterial surface. Transcriptome studies reveal that ZGNFs can disorder basic metabolic processes of Methicillin-resistant Staphylococcus aureus (MRSA). Moreover, in a MRSA-induced keratitis model, ZGNFs exhibit long-term retention in the infected corneal site and prominent MRSA elimination efficacy due to the self-targeting ability. This research not only reports an innovative method to prepare metal-polyphenol nanoparticles, but also provides a novel nanoplatform for targeted delivery of Zn2+ in combating Gram-positive bacterial infections.

Zn-Shik-PEG nanoparticles alleviate inflammation and multi-organ damage in sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by excessive formation of reactive oxygen species (ROS) and dysregulated inflammatory response. Previous studies have reported that shikonin (Shik) possess prominent anti-inflammatory and antioxidant effects and holds promise as a potential therapeutic drug for sepsis. However, the poor water solubility and the relatively high toxicity of shikonin hamper its clinical application. To address this challenge, we constructed Zn2+-shikonin nanoparticles, hereafter Zn-Shik-PEG NPs, based on an organic-inorganic hybridization strategy of metal-polyphenol coordination to improve the aqueous solubility and biosafety of shikonin. Mechanistic studies suggest that Zn-Shik-PEG NPs could effectively clear intracellular ROS via regulating the Nrf2/HO-1 pathway, meanwhile Zn-Shik-PEG NPs could inhibit NLRP3 inflammasome-mediated activation of inflammation and apoptosis by regulating the AMPK/SIRT1 pathway. As a result, the Zn-Shik-PEG NPs demonstrated excellent therapeutic efficacies in lipopolysaccharide (LPS) as well as cecal ligation puncture (CLP) induced sepsis model. These findings suggest that Zn-Shik-PEG NPs may have therapeutic potential for the treatment of other ROS-associated and inflammatory diseases.

Cyclodextrin-Derived ROS-Generating Nanomedicine with pH-Modulated Degradability to Enhance Tumor Ferroptosis Therapy and Chemotherapy.

Nowadays, destruction of redox homeostasis to induce cancer cell death is an emerging anti-cancer strategy. Here, the authors utilized pH-sensitive acetalated ß-cyclodextrin (Ac-ß-CD) to efficiently deliver dihydroartemisinin (DHA) for tumor ferroptosis therapy and chemodynamic therapy in a synergistic manner. The Ac-ß-CD-DHA based nanoparticles are coated by an iron-containing polyphenol network. In response to the tumor microenvironment, Fe2+ /Fe3+ can consume glutathione (GSH) and trigger the Fenton reaction in the presence of hydrogen peroxide (H2 O2 ), leading to the generation of lethal reactive oxygen species (ROS). Meanwhile, the OO bridge bonds of DHA are also disintegrated to enable ferroptosis of cancer cells. Their results demonstrate that these nanoparticles acted as a ROS generator to break the redox balance of cancer cells, showing an effective anticancer efficacy, which is different from traditional approaches.

Material priority engineered metal-polyphenol networks: mechanism and platform for multifunctionalities.

Engineering the surface of materials with desired multifunctionalities is an effective way to fight against multiple adverse factors during tissue repair process. Recently, metal-polyphenol networks (MPNs) have gained increasing attention because of their rapid and simple deposition process onto various substrates (silicon, quartz, gold and polypropylene sheets, etc.). However, the coating mechanism has not been clarified, and multifunctionalized MPNs remain unexplored. Herein, the flavonoid polyphenol procyanidin (PC) was selected to form PC-MPN coatings with Fe3+, and the effects of different assembly parameters, including pH, molar ratio between PC and Fe3+, and material priority during coating formation, were thoroughly evaluated. We found that the material priority (addition sequence of PC and Fe3+) had a great influence on the thickness of the formed PC-MPNs. Various surface techniques (e.g., ultraviolet-visible spectrophotometry, quartz crystal microbalance, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy) were used to investigate the formation mechanism of PC-MPNs. Then PC-MPNs were further engineered with multifunctionalities (fastening cellular attachment in the early stage, promoting long-term cellular proliferation, antioxidation and antibacterial activity). We believe that these findings could further reveal the coating formation mechanism of MPNs and guide the future design of MPN coatings with multifunctionalities, thereby greatly broadening their application prospects, such as in sensors, environments, drug delivery, and tissue engineering.

Polyphenol-Based Nanomedicine Evokes Immune Activation for Combination Cancer Treatment.

Engineering multifunctional nanoplatforms with high therapeutic benefits has become a promising strategy for intractable cancer treatment. A novel polyphenol-based nanocomplex was designed to evoke highly efficacious cancer immunosurveillance while localizing therapy on the primary tumor and to minimize systemic side effects. This nanocomplex is prepared via metal-polyphenol coordination by encapsulating a natural polyphenol, gossypol, and a newly synthesized polyphenol derivative, polyethylene glycol-Chlorin e6 (Ce6). The combination of gossypol from cotton and the photosensitizer Ce6 can induce chemotherapeutic/photodynamic immunogenic cancer cell death upon laser irradiation, which is supported by a rich maturation of dendritic cells, concentrated secretion of inflammatory cytokines, and significant inhibition of distant untreated tumors. Finally, an assistance of the programmed-cell-death ligand-1 checkpoint-blockade immunotherapy can enhance the anti-tumor immune stimulation of our nanoplatform to a higher level.

An Adenosine Triphosphate-Responsive Autocatalytic Fenton Nanoparticle for Tumor Ablation with Self-Supplied H2O2 and Acceleration of Fe(III)/Fe(II) Conversion.

Chemodynamic therapy (CDT) can efficiently destroy tumor cells via Fenton reaction in the presence of H2O2 and a robust catalyst. However, it has faced severe challenges including the limited amounts of H2O2 and inefficiency of catalysts. Here, an adenosine triphosphate (ATP)-responsive autocatalytic Fenton nanosystem (GOx@ZIF@MPN), incorporated with glucose oxidase (GOx) in zeolitic imidazolate framework (ZIF) and then coated with metal polyphenol network (MPN), was designed and synthesized for tumor ablation with self-supplied H2O2 and TA-mediated acceleration of Fe(III)/Fe(II) conversion. In the ATP-overexpressed tumor cells, the outer shell MPN of GOx@ZIF@MPN was degraded into Fe(III) and tannic acid (TA) and the internal GOx was exposed. Then, GOx reacted with the endogenous glucose to produce plenty of H2O2, and TA reduced Fe(III) to Fe(II), which is a much more vigorous catalyst for the Fenton reaction. Subsequently, self-produced H2O2 was catalyzed by Fe(II) to generate highly toxic hydroxyl radical (•OH) and Fe(III). The produced Fe(III) with low catalytic activity was quickly reduced to reactive Fe(II) mediated by TA, forming an accelerated Fe(III)/Fe(II) conversion to guarantee efficient Fenton reaction-mediated CDT. This autocatalytic Fenton nanosystem might provide a good paradigm for effective tumor treatment.

Iron-based magnetic nanocomplexes for combined chemodynamic and photothermal cancer therapy through enhanced ferroptosis.

Chemodynamic therapy (CDT) guided by Fenton chemistry and iron-containing materials can induce ferroptosis as a prospective cancer treatment method, but the inefficient Fe3+/Fe2+ conversion restricts the monotherapeutic performances. Here, an iron-based nanoplatform (Fe3O4-SRF@FeTA) including a magnetic core and a reductive film is developed for combined CDT and photothermal therapy (PTT) through ferroptosis augmentation. The inner iron oxide core serves as a photothermal transducer, a magnet-responsive module, and an iron reservoir for CDT. The coated Fe3+-tannic acid film (FeTA) provides extra iron and reductants for Fe3+/Fe2+ conversion acceleration, and functions as a door keeper for the pH- and light-responsive release of the embedded ferroptosis inducer sorafenib (SRF). The in vitro results demonstrate that the iron-based nanocomplexes promote the production of lipid peroxide through the amplified Fenton activity, and downregulate glutathione involved in lipid peroxide repair system through the responsively released SRF. Upon accumulation in tumor by magnetic targeting and sequential laser irradiation locoregionally, Fe3O4-SRF@FeTA nanocomplexes present prominent in vivo anticancer efficacy by leveraging PTT and CDT-enhanced ferroptosis.

Multi-mechanism antitumor/antibacterial effects of Cu-EGCG self-assembling nanocomposite in tumor nanotherapy and drug-resistant bacterial wound infections.

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.

Metal-polyphenol self-assembled nanodots for NIR-II fluorescence imaging-guided chemodynamic/photodynamic therapy-amplified ferroptosis.

The effectiveness of tumor treatment using reactive oxygen species as the primary therapeutic medium is hindered by limitations of tumor microenvironment (TME), such as intrinsic hypoxia in photodynamic therapy (PDT) and overproduction of reducing glutathione (GSH) in chemodynamic therapy (CDT). Herein, we fabricate metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging. The Fe@BDP NDs are designed for synergistic combination of type-I PDT and CDT-amplified ferroptosis. In a mildly acidic TME, Fe@BDP NDs demonstrate great Fenton activity, leading to the generation of highly toxic hydroxyl radicals from overproduced hydrogen peroxide in tumor cells. Furthermore, Fe@BDP NDs show favorable efficacy in type-I PDT, even in tolerating tumor hypoxia, generating active superoxide anion upon exposure to 808 nm laser irradiation. The significant efficiency in reactive oxygen species (ROS) products results in the oxidation of sensitive polyunsaturated fatty acids, accelerating lethal lipid peroxidation (LPO) bioprocess. Additionally, Fe@BDP NDs illustrate an outstanding capability for GSH depletion, causing the inactivation of glutathione peroxidase 4 and further promoting lethal LPO. The synergistic type-I photodynamic and chemodynamic cytotoxicity effectively trigger irreversible ferroptosis by disrupting the intracellular redox homeostasis. Moreover, Fe@BDP NDs demonstrate charming NIR-II fluorescence imaging capability and effectively accumulated at the tumor site, visualizing the distribution of Fe@BDP NDs and the treatment process. The chemo/photo-dynamic-amplified ferroptotic efficacy of Fe@BDP NDs was evidenced both in vitro and in vivo. This study presents a compelling approach to intensify ferroptosis via visualized CDT and PDT. STATEMENT OF SIGNIFICANCE: In this study, we detailed the fabrication of metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging, aiming to intensify ferroptosis via the synergistic combination of type-I PDT and CDT. In a mildly acidic TME, Fe@BDP NDs exhibited significant Fenton activity, resulting in the generation of highly toxic •OH from overproduced H2O2 in tumor cells. Fe@BDP NDs possessed a remarkable capability for GSH depletion, resulting in the inactivation of glutathione peroxidase 4 (GPX4) and further accelerating lethal LPO. This study presented a compelling approach to intensify ferroptosis via visualized CDT and PDT.

Preparation and characterization of metal-polyphenol networks encapsulated in sodium alginate microbead hydrogels for catechin and vitamin C delivery.

A novel encapsulation system was designed, utilizing sodium alginate (SA) polysaccharide as the matrix and easily absorbed Fe2+ as the metal-organic framework, to construct microbead scaffolds with both high catechins (CA) and vitamin C (Vc) loading and antioxidant properties. The structure of microbead hydrocolloids was investigated using SEM, XPS, FTIR, XRD and thermogravimetry, and the antioxidant activity, in vitro digestion and the release of CA and Vc were evaluated. These results revealed that the microbead hydrocolloids SA-CA-Fe and SA-CA-Vc-Fe exhibited denser and stronger cross-linking structures, and the formation of inter- and intramolecular hydrogen and coordination bonds improved thermal stability. Moreover, SA-CA-Fe (44.9 % DPPH and 47.8 % ABTS) and SA-CA-Vc-Fe (89.9 % DPPH and 89.3 % ABTS) displayed strong antioxidant activity. Importantly, they were non-toxic in Caco2 cells. The SA-CA-Fe and SA-CA-Vc-Fe achieved significantly higher CA (56.9 and 62.7 %, respectively) and Vc (42.2 %) encapsulation efficiency while maintaining higher CA and Vc release in small intestinal environment. These results suggested that SA polysaccharide-based encapsulation system using Fe2+ framework as scaffold had greater potential for delivery and controlled release of CA and Vc than conventional hydrocolloids, which could provide new insights into the construction of high loading, safe, targeted polyphenol delivery system.

Multifunctional iron-apigenin nanocomplex conducting photothermal therapy and triggering augmented immune response for triple negative breast cancer.

Triple negative breast cancer (TNBC) presents a formidable challenge due to its low sensitivity to many chemotherapeutic drugs and a relatively low overall survival rate in clinical practice. Photothermal therapy has recently garnered substantial interest in cancer treatment, owing to its swift therapeutic effectiveness and minimal impact on normal cells. Metal-polyphenol nanostructures have recently garnered significant attention as photothermal transduction agents due to their facile preparation and favorable photothermal properties. In this study, we employed a coordinated approach involving Fe3+ and apigenin, a polyphenol compound, to construct the nanostructure (nFeAPG), with the assistance of ß-CD and DSPE-PEG facilitating the formation of the complex nanostructure. In vitro research demonstrated that the formed nFeAPG could induce cell death by elevating intracellular oxidative stress, inhibiting antioxidative system, and promoting apoptosis and ferroptosis, and near infrared spectrum irradiation further strengthen the therapeutic outcome. In 4T1 tumor bearing mice, nFeAPG could effectively accumulate into tumor site and exhibit commendable control over tumor growth. Futher analysis demonstrated that nFeAPG ameliorated the suppressed immune microenvironment by augmenting the response of DC cells and T cells. This study underscores that nFeAPG encompasses a multifaceted capacity to combat TNBC, holding promise as a compelling therapeutic strategy for TNBC treatment.

Polyphenol-mediated defect patching of graphene oxide membranes for sulfonamide contaminants removal and fouling control.

Graphene oxide (GO)-based laminar membranes are promising candidates for next-generation nanofiltration membranes because of their theoretically frictionless nanochannels. However, nonuniform stacking during the filtration process and the inherent swelling of GO nanosheets generate horizontal and vertical defects, leading to a low selectivity and susceptibility to pore blockage. Herein, both types of defects are simultaneously patching by utilizing tannic acid and FeⅢ. Tannic acid first partially reduced the upper GO framework, and then coordinated with FeⅢ to form a metal-polyphenol network covering horizontal defects. Due to the enhanced steric hindrance, the resulting membrane exhibited a two-fold increase in sulfonamide contaminants exclusion compared to the pristine GO membrane. A non-significant reduction in permeance was observed. In terms of fouling control, shielding defects significantly alleviated the irreversible pore blockage of the membrane. Additionally, the hydrophilic metal-polyphenol network weakened the adhesion force between the membrane and foulants, thereby improving the reversibility of fouling in the cleaning stage. This work opens up a new way to develop GO-based membranes with enhanced separation performance and antifouling ability.

Engineering M2-type macrophages with a metal polyphenol network for peripheral artery disease treatment.

Functional cell treatment for critical limb ischemia is limited by cell viability loss and dysfunction resulting from a harmful ischemic microenvironment. Metal-polyphenol networks have emerged as novel cell delivery vehicles for protecting cells from the detrimental ischemic microenvironment and prolonging the survival rate of cells in the ischemic microenvironment. M2 macrophages are closely related to tissue repair, and they secrete anti-inflammatory factors that contribute to lesion repair. However, these cells are easily metabolized in the body with low efficiency. Herein, M2 macrophages were decorated with a metal‒polyphenol network that contains copper ions and epigallocatechin gallate (Cu-EGCG@M2) to increase cell survival and therapeutic potential. Cu-EGCG@M2 synergistically promoted angiogenesis through the inherent angiogenesis effect of M2 macrophages and copper ions. We found that Cu-EGCG@M2 increased in vitro viability and strengthened the in vivo therapeutic effect on the ischemic hindlimbs of mice, which promoted the recovery of blood and muscle regeneration, resulting in superior limb salvage. These therapeutic effects were ascribed to the increased survival rate and therapeutic period of M2 macrophages, as well as the ameliorated microenvironment at the ischemic site. Additionally, Cu-EGCG exhibited antioxidant, anti-inflammatory, and proangiogenic effects. Our findings provide a feasible option for cell-based treatment of CLI.

Augmented the sensitivity of photothermal-ferroptosis therapy in triple-negative breast cancer through mitochondria-targeted nanoreactor.

Ferroptosis primarily relies on reactive oxygen (ROS) production and lipid peroxide (LPO) accumulation, which opens up new opportunities for tumor therapy. However, a standalone ferroptosis process is insufficient in inhibiting tumor progression. Unlike previously reported Fe-based nanomaterials, we have engineered a novel nanoreactor named IR780/Ce@EGCG/APT, which uses metal-polyphenols network (Ce@EGCG) based on rare-earth cerium and epigallocatechin gallate (EGCG) to encapsulate IR780 and modified with the aptamer (AS1411). The intricately designed nanoreactor is specifically taken up by tumor cells, releasing Ce3+, EGCG, and IR780. On the one hand, Ce3+ triggers ROS production via a Fenton-like reaction, inducing ferroptosis in tumor cells. On the other hand, IR780 accumulates in mitochondria and disrupts mitochondrial function upon laser irradiation, leading to tumor cell apoptosis. EGCG serves as a sensitizer, simultaneously enhancing the sensitivity of tumor cells to ferroptosis and photothermal therapy. After a single dose and three times of 808 nm laser irradiation for treatment, it has been observed that the nanoreactor induces dendritic cells (DCs) maturation, facilitates cytotoxic T lymphocyte infiltration, improves immunosuppressive microenvironment, activates the systemic immune system, and generates long-term immune memory.

Development of a Controllable Intelligent Drug Delivery System for Efficient Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.

Dual-responsive nanoplatform for integrated cancer diagnosis and therapy: Unleashing the power of tumor microenvironment.

Chemodynamic therapy (CDT), designed to trigger a tumor-specific hydrogen peroxide (H2O2) reaction generating highly toxic hydroxyl radicals (·OH), has been investigated for cancer treatment. Unfortunately, the limited Fenton or Fenton-like reaction rate and the significant impact of excessive reducing glutathione (GSH) in the tumor microenvironment (TME) have severely compromised the effectiveness of CDT. To address this issue, we designed a dual-responsive nanoplatform utilizing a metal-polyphenol network (MPN) -coated multi-caged IrOx for efficient anti-tumor therapy in response to the acidic TME and intracellular excess of GSH, in which MPN composed of Fe3+ and tannic acid (TA). Initially, the acidic TME and intracellular excess of GSH lead to the degradation of the MPN shell, resulting in the release of Fe3+ and exposure of the IrOx core, facilitating the efficient dual-pathway CDT. Subsequently, the nanoplatform can mitigate the attenuation of CDT by consuming the excessive GSH within the tumor. Finally, the multi-caged structure of IrOx is advantageous for effectively implementing photothermal therapy (PTT) in coordination with CDT, further enhancing the therapeutic efficacy of tumors. Moreover, the outstanding Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) (T1/T2) multimodal imaging capabilities of IrOx@MPN enable early diagnosis and timely treatment. This work provides a typical example of the construction of a novel multifunctional platform for dual-responsive treatment of tumors.

Photoactive Poly-L-Lysine gel with resveratrol-magnesium metal polyphenol network: A promising strategy for preventing tracheal anastomotic complications following surgery.

Postoperative complications at the anastomosis site following tracheal resection are a prevalent and substantial concern. However, most existing solutions primarily focus on managing symptoms, with limited attention given to proactively preventing the underlying pathological processes. To address this challenge, we conducted a drug screening focusing on clinically-relevant polyphenolic compounds, given the growing interest in polyphenolic compounds for their potential role in tissue repair during wound healing. This screening led to the identification of resveratrol as the most promising candidate for mitigating tracheal complications, as it exhibited the most significant efficacy in enhancing the expression of vascular endothelial growth factor (VEGF) while concurrently suppressing the pivotal fibrosis factor: transforming growth factor-beta 1 (TGF-ß1), showcasing its robust potential in addressing these issues. Building upon this discovery, we further developed an innovative photosensitive poly-L-lysine gel integrated with a resveratrol-magnesium metal polyphenol network (MPN), named Res-Mg/PL-MA. This design allows for the enables sustained release of resveratrol and synergistically enhances the expression of VEGF and also promotes resistance to tensile forces, aided by magnesium ions, in an anastomotic tracheal fistula animal models. Moreover, the combination of resveratrol and poly-L-lysine hydrogel effectively inhibits bacteria, reduces local expression of key inflammatory factors, and induces polarization of macrophages toward an anti-inflammatory phenotype, as well as inhibits TGF-ß1, consequently decreasing collagen production levels in an animal model of post-tracheal resection. In summary, our novel Res-Mg/PL-MA hydrogel, through antibacterial, anti-inflammatory, and pro-vascularization mechanisms, effectively prevents complications at tracheal anastomosis, offering significant promise for translational applications in patients undergoing tracheal surgeries.

GSH responsive AuNRs@TFF nanotheranostic for NIR-II photoacoustic imaging-guided CDT/PTT synergistic cancer therapy.

Gold nanorods (AuNRs) are important photothermal therapeutic agents; however, a single therapy does not achieve satisfactory outcomes, and the synthesis process often leads to the adsorption of cetyltrimethylammonium bromide on the surface of AuNRs, which reduces its biocompatibility. Natural polyphenols are abundant in natural plants and have good biocompatibility. The metal-polyphenol network is formed by the coordination of metal ions and polyphenols, which has good drug loading, surface adhesion, and biocompatibility. In this study, the metal-polyphenol network structure formed by a transition metal (iron) and natural polyphenol tannic acid was used to modify the surface of gold nanorods (AuNRs@TF). Additionally, the surfaces of AuNRs were modified using the targeted functional molecule mercapto folic acid (AuNRs@TFF). The constructed composite nanomaterials AuNRs@TFF has good biocompatibility and tumor targeting ability. Tannic acid­iron degrades in the tumor microenvironment and releases iron ions that catalyze the Fenton reaction, thereby facilitating chemodynamic therapy. The good photo-thermal ability of AuNRs generate good photoacoustic signals to facilitate photoacoustic imaging mediation and enhances photothermal and chemodynamic therapy performance. This study expands on the application of AuNRs in the field of nanomedicine. The simple and effective design of AuNRs@TFF provides a strategy for the development of synergistic therapeutic agents for photothermal therapy and chemodynamic therapy.

Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia-reperfusion injury.

Aim: To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA).Materials & methods: After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosis and apoptosis, as well as injury severity.Results: Malondialdehyde, Fe2+ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn2+ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROS scavenging and cell-death inhibition.Conclusion: This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.

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