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1.
Anal Chem ; 96(19): 7697-7705, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38697043

RESUMO

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.


Assuntos
Elementos da Série dos Lantanídeos , Imageamento por Ressonância Magnética , Nanopartículas , Polímeros , Semicondutores , Imageamento por Ressonância Magnética/métodos , Animais , Elementos da Série dos Lantanídeos/química , Polímeros/química , Nanopartículas/química , Camundongos , Humanos , Gadolínio/química , Luminescência , Oxigênio Singlete/química , Ítrio/química , Fluoretos/química , Camundongos Nus
2.
J Ethnopharmacol ; 328: 118108, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38574780

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala fallax Hemsl. is a traditional folk medicine commonly used by ethnic minorities in the Guangxi Zhuang Autonomous Region, and has a traditional application in the treatment of liver disease. Polygala fallax Hemsl. polysaccharides (PFPs) are of interest for their potential health benefits. AIM OF THIS STUDY: This study explored the impact of PFPs on a mouse model of cholestatic liver injury (CLI) induced by alpha-naphthyl isothiocyanate (ANIT), as well as the potential mechanisms. MATERIALS AND METHODS: A mouse CLI model was constructed using ANIT (80 mg/kg) and intervened with different doses of PFPs or ursodeoxycholic acid. Their serum biochemical indices, hepatic oxidative stress indices, and hepatic pathological characteristics were investigated. Then RNA sequencing was performed on liver tissues to identify differentially expressed genes and signaling pathways and to elucidate the mechanism of liver protection by PFPs. Finally, Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to verify the differentially expressed genes. RESULTS: Data analyses showed that PFPs reduced the levels of liver function-related biochemical indices, such as ALT, AST, AKP, TBA, DBIL, and TBIL. PFPs up-regulated the activities of SOD and GSH, down-regulated the contents of MDA, inhibited the release of IL-1ß, IL-6, and TNF-α, or promoted IL-10. Pathologic characterization of the liver revealed that PFPs reduced hepatocyte apoptosis or necrosis. The RNA sequencing indicated that the genes with differential expression were primarily enriched for the biosynthesis of primary bile acids, secretion or transportation of bile, the reactive oxygen species in chemical carcinogenesis, and the NF-kappa B signaling pathway. In addition, the results of qRT-PCR and Western blotting analysis were consistent with those of RNA sequencing analysis. CONCLUSIONS: In summary, this study showed that PFPs improved intrahepatic cholestasis and alleviated liver damage through the modulation of primary bile acid production, Control of protein expression related to bile secretion or transportation, decrease in inflammatory reactions, and inhibition of oxidative pressure. As a result, PFPs might offer a hopeful ethnic dietary approach for managing intrahepatic cholestasis.


Assuntos
Colestase Intra-Hepática , Colestase , Polygala , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , 1-Naftilisotiocianato/toxicidade , China , Fígado/metabolismo , Colestase/induzido quimicamente , Colestase/tratamento farmacológico , Colestase/metabolismo , Colestase Intra-Hepática/induzido quimicamente , Isotiocianatos/efeitos adversos , Isotiocianatos/metabolismo , Ácidos e Sais Biliares/metabolismo
3.
J Am Chem Soc ; 146(9): 6252-6265, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38377559

RESUMO

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.


Assuntos
Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio , Antracenos , Linhagem Celular Tumoral
4.
Artigo em Inglês | MEDLINE | ID: mdl-37752407

RESUMO

Magnetic resonance imaging (MRI) is a non-invasive, radiation-free imaging technique widely used for disease detection and therapeutic evaluation due to its infinite penetration depth. Magnetic nanoparticles (MNPs) have unique magnetic and physicochemical properties, making them ideal as contrast agents for MRI. However, the in vivo toxicity of MNPs, resulting from metal ion leakage and long-term accumulation in the reticuloendothelial system (RES), limits their clinical application. To overcome these challenges, there is considerable interest in the development of renal-clearable MNPs that can be completely cleared through the kidney, reducing retention time and potential toxic risks. In this review, we provide an overview of recent advancements in the development of renal-clearable MNPs for disease imaging and treatment. We discuss the factors influencing renal clearance, summarize the types of renal-clearable MNPs, their synthesis methods, and biomedical applications. This review aims to offer comprehensive information for the design and clinical translation of renal-clearable MNPs. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.


Assuntos
Nanopartículas de Magnetita , Nanopartículas de Magnetita/química , Meios de Contraste/química , Nanotecnologia , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
5.
Sci Bull (Beijing) ; 69(5): 636-647, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38158292

RESUMO

Lipid peroxidation (LPO), the process of membrane lipid oxidation, is a potential new form of cell death for cancer treatment. However, the radical chain reaction involved in LPO is comprised of the initiation, propagation (the slowest step), and termination stages, limiting its effectiveness in vivo. To address this limitation, we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation, thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes. Firstly, radical chain transfer agent (CTA-1)/Fe nanoparticles (CTA-Fe NPs-1) was synthesized. Notably, CTA-1 convert low activity peroxyl radicals (ROO·) into high activity alkoxyl radicals (RO·), creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation. Additionally, CTA-1/Fe ions enhance reactive oxygen species (ROS) generation, consume glutathione (GSH), and thereby inactivate GPX-4, promoting the initiation stage and reducing termination of free radical reaction. CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes, leading to highly effective treatment in cancer cells. In addition, CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging (MRI). In summary, CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation, propagation, and inhibiting termination step, promoting the cycle of free radical reaction, resulting in effective anticancer outcomes in tumor-bearing mice.


Assuntos
Glutationa , Neoplasias , Camundongos , Animais , Peroxidação de Lipídeos , Oxirredução , Radicais Livres/metabolismo , Espécies Reativas de Oxigênio , Glutationa/metabolismo , Neoplasias/diagnóstico por imagem
6.
Foods ; 12(21)2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37959146

RESUMO

Ultrasound has been widely used as a green and efficient non-thermal processing technique to assist with enzymatic hydrolysis. Compared with traditional enzymatic hydrolysis, ultrasonic-pretreatment-assisted enzymatic hydrolysis can significantly improve the efficiency of enzymatic hydrolysis and enhance the biological activity of substrates. At present, this technology is mainly used for the extraction of bioactive substances and the degradation of biological macromolecules. This review is focused on the mechanism of enzymatic hydrolysis assisted by ultrasonic pretreatment, including the effects of ultrasonic pretreatment on the enzyme structure, substrate structure, enzymatic hydrolysis kinetics, and thermodynamics and the effects of the ultrasonic conditions on the enzymatic hydrolysis results. The development status of ultrasonic devices and the application of ultrasonic-assisted enzymatic hydrolysis in the food industry are briefly described in this study. In the future, more attention should be paid to research on ultrasound-assisted enzymatic hydrolysis devices to promote the expansion of production and improve production efficiency.

7.
J Nanobiotechnology ; 21(1): 434, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980476

RESUMO

Manganese-based nanomaterials (Mn-nanomaterials) hold immense potential in cancer diagnosis and therapies. However, most Mn-nanomaterials are limited by the low sensitivity and low efficiency toward mild weak acidity (pH 6.4-6.8) of the tumor microenvironment, resulting in unsatisfactory therapeutic effect and poor magnetic resonance imaging (MRI) performance. This study introduces pH-ultrasensitive PtMn nanoparticles as a novel platform for enhanced ferroptosis-based cancer theranostics. The PtMn nanoparticles were synthesized with different diameters from 5.3 to 2.7 nm with size-dominant catalytic activity and magnetic relaxation, and modified with an acidity-responsive polymer to create pH-sensitive agents. Importantly, R-PtMn-1 (3 nm core) presents "turn-on" oxidase-like activity, affording a significant enhancement ratio (pH 6.0/pH 7.4) in catalytic activity (6.7 folds), compared with R-PtMn-2 (4.2 nm core, 3.7 folds) or R-PtMn-3 (5.3 nm core, 2.1 folds), respectively. Moreover, R-PtMn-1 exhibits dual-mode contrast in high-field MRI. R-PtMn-1 possesses a good enhancement ratio (pH 6.4/pH 7.4) that is 3 or 3.2 folds for T1- or T2-MRI, respectively, which is higher than that of R-PtMn-2 (1.4 or 1.5 folds) or R-PtMn-3 (1.1 or 1.2 folds). Moreover, their pH-ultrasensitivity enabled activation specifically within the tumor microenvironment, avoiding off-target toxicity in normal tissues during delivery. In vitro studies demonstrated elevated intracellular reactive oxygen species production, lipid peroxidation, mitochondrial membrane potential changes, malondialdehyde content, and glutathione depletion, leading to enhanced ferroptosis in cancer cells. Meanwhile, normal cells remained unaffected by the nanoparticles. Overall, the pH-ultrasensitive PtMn nanoparticles offer a promising strategy for accurate cancer diagnosis and ferroptosis-based therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Manganês/química , Medicina de Precisão , Meios de Contraste/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral
8.
Exploration (Beijing) ; 3(3): 20220002, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37933379

RESUMO

The acidic characteristic of the tumor site is one of the most well-known features and provides a series of opportunities for cancer-specific theranostic strategies. In this regard, pH-responsive theranostic nanoplatforms that integrate diagnostic and therapeutic capabilities are highly developed. The fluidity of the tumor microenvironment (TME), with its temporal and spatial heterogeneities, makes noninvasive molecular magnetic resonance imaging (MRI) technology very desirable for imaging TME constituents and developing MRI-guided theranostic nanoplatforms for tumor-specific treatments. Therefore, various MRI-based theranostic strategies which employ assorted therapeutic modes have been drawn up for more efficient cancer therapy through the raised local concentration of therapeutic agents in pathological tissues. In this review, we summarize the pH-responsive mechanisms of organic components (including polymers, biological molecules, and organosilicas) as well as inorganic components (including metal coordination compounds, metal oxides, and metal salts) of theranostic nanoplatforms. Furthermore, we review the designs and applications of pH-responsive theranostic nanoplatforms for the diagnosis and treatment of cancer. In addition, the challenges and prospects in developing theranostic nanoplatforms with pH-responsiveness for cancer diagnosis and therapy are discussed.

9.
Oncol Rep ; 50(6)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37859622

RESUMO

Lung squamous cell carcinoma (LSCC) is a highly heterogeneous malignancy with high mortality and few therapeutic options. Licochalcone A (LCA, PubChem ID: 5318998) is a chalcone extracted from licorice and possesses anticancer and anti­inflammatory activities. The present study aimed to elucidate the anticancer effect of LCA on LSCC and explore the conceivable molecular mechanism. MTT assay revealed that LCA significantly inhibited the proliferation of LSCC cells with less cytotoxicity towards human bronchial epithelial cells. 5­ethynyl­2'­deoxyuridine (EdU) assay demonstrated that LCA could reduce the proliferation rate of LSCC cells. The flow cytometric assays indicated that LCA increased the cell number of the G1 phase and induced the apoptosis of LSCC cells. LCA downregulated the protein expression of cyclin D1, cyclin E, CDK2 and CDK4. Meanwhile, LCA increased the expression level of Bax, cleaved poly(ADP­ribose)polymerase­1 (PARP1) and caspase 3, as well as downregulated the level of Bcl­2. Proteomics assay demonstrated that LCA exerted its antitumor effects via inhibiting mitogen­activated protein kinase (MAPK) signaling pathways and the expression of F­box protein 5 (FBXO5). Western blot analysis showed that LCA decreased the expression of p­ERK1/2, p­p38MAPK and FBXO5. In the xenograft tumors of LSCC, LCA significantly inhibited the volumes and weight of tumors in nude mice with little toxicity in vital organs. Therefore, the present study demonstrated that LCA effectively inhibited cell proliferation and induced apoptosis in vitro, and suppressed xenograft tumor growth in vivo. LCA may serve as a future therapeutic candidate of LSCC.


Assuntos
Carcinoma de Células Escamosas , Chalconas , Proteínas F-Box , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Chalconas/farmacologia , Chalconas/uso terapêutico , Proteínas F-Box/metabolismo , Pulmão/patologia , Camundongos Nus , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo
10.
ACS Nano ; 17(14): 13792-13810, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37458417

RESUMO

Ferroptosis, as a type of programmed cell death process, enables effective damage to various cancer cells. However, we discovered that persistent oxidative stress during ferroptosis can upregulate the apurinic/apyrimidinic endonuclease 1 (APE1) protein that induces therapeutic resistance ("ferroptosis resistance"), resulting in an unsatisfactory treatment outcome. To address APE1-induced therapeutic resistance, we developed a GSH/APE1 cascade activated therapeutic nanoplatform (GAN). Specifically, the GAN is self-assembled by DNA-functionalized ultrasmall iron oxide nanoparticles and further loaded with drug molecules (drug-GAN). GSH-triggered GAN disassembly can "turn on" the catalysis of GAN to induce efficient lipid peroxidation (LPO) for ferroptosis toward the tumor, which could upregulate APE1 expression. Subsequently, upregulated APE1 can further trigger accurate drug release for overcoming ferroptosis resistance and inducing the recovery of near-infrared fluorescence for imaging the dynamics of APE1. Importantly, adaptive drug release can overcome the adverse effects of APE1 upregulation by boosting intracellular ROS yield and increasing DNA damage, to offset APE1's functions of antioxidant and DNA repair, thus leading to adaptive ferroptosis. Moreover, with overexpressed GSH and upregulated APE1 in the tumor as stimuli, the therapeutic specificity of ferroptosis toward the tumor is greatly improved, which minimized nonspecific activation of catalysis and excessive drug release in normal tissues. Furthermore, a switchable MRI contrast from negative to positive is in sync with ferroptosis activation, which is beneficial for monitoring the ferroptosis process. Therefore, this adapted imaging and therapeutic nanoplatform can not only deliver GSH/APE1-activated lipid peroxide mediated adaptive synergistic therapy but also provided a switchable MRI/dual-channel fluorescence signal for monitoring ferroptosis activation, drug release, and therapy resistance dynamics in vivo, leading to high-specificity and high-efficiency adaptive ferroptosis therapy.


Assuntos
Ferroptose , Neoplasias , Humanos , Endonucleases , Reparo do DNA , Estresse Oxidativo , Linhagem Celular Tumoral
11.
Nutrients ; 15(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37375702

RESUMO

Ancientino, a complex dietary fiber supplement mimicking the ancient diet, has improved chronic heart failure, kidney function, and constipation. However, its effect on ulcerative colitis is unknown. This study explores the impact of Ancientino on colitis caused by dextran sulfate sodium (DSS) and its mechanisms. Data analyses showed that Ancientino alleviated bodyweight loss, colon shortening and injury, and disease activity index (DAI) score, regulated levels of inflammatory factors (tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-1 beta (IL-1ß), and interleukin 6 (IL-6)), reduced intestinal permeability (d-lactate and endotoxin), fluorescein isothiocyanate-dextran (FITC-dextran), and diamine oxidase (DAO), repaired colonic function (ZO-1 and occludin), and suppressed oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA)) in vivo and in vitro. In short, this study demonstrated that Ancientino alleviates colitis and exerts an anticolitis effect by reducing inflammatory response, suppressing oxidative stress, and repairing intestinal barrier function. Thus, Ancientino may be an effective therapeutic dietary resource for ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Dextranos/uso terapêutico , Colite/tratamento farmacológico , Inflamação/metabolismo , Colo/metabolismo , Estresse Oxidativo , Interleucina-6/metabolismo , Suplementos Nutricionais , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
12.
ACS Nano ; 17(10): 9529-9542, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37154230

RESUMO

Hepatic ischemia-reperfusion (I/R) injury accompanied by oxidative stress is responsible for postoperative liver dysfunction and failure of liver surgery. However, the dynamic non-invasive mapping of redox homeostasis in deep-seated liver during hepatic I/R injury remains a great challenge. Herein, inspired by the intrinsic reversibility of disulfide bond in proteins, a kind of reversible redox-responsive magnetic nanoparticles (RRMNs) is designed for reversible imaging of both oxidant and antioxidant levels (ONOO-/GSH), based on sulfhydryl coupling/cleaving reaction. We develop a facile strategy to prepare such reversible MRI nanoprobe via one-step surface modification. Owing to the significant change in size during the reversible response, the imaging sensitivity of RRMNs is greatly improved, which enables RRMNs to monitor the tiny change of oxidative stress in liver injury. Notably, such reversible MRI nanoprobe can non-invasively visualize the deep-seated liver tissue slice by slice in living mice. Moreover, this MRI nanoprobe can not only report molecular information about the degree of liver injury but also provide anatomical information about where the pathology occurred. The reversible MRI probe is promising for accurately and facilely monitoring I/R process, accessing injury degree and developing powerful strategy for precise treatment.


Assuntos
Hepatopatias , Traumatismo por Reperfusão , Camundongos , Animais , Fígado/metabolismo , Traumatismo por Reperfusão/metabolismo , Hepatopatias/metabolismo , Estresse Oxidativo , Oxirredução , Imageamento por Ressonância Magnética
13.
J Mater Chem B ; 11(26): 5933-5952, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37254674

RESUMO

Nanozymes are nanoscale materials that display enzyme-like properties, which have been improved to eliminate the limitations of natural enzymes and further broaden the use of conventional artificial enzymes. In the last decade, the research and exploration of nanozymes have attracted considerable attention in the chemical and biological fields, especially in the fields of biomedicine and tumor therapy. To date, plenty of nanozymes have been developed with the single or multiple activities of natural enzymes, including peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), glucose oxidase (GOx). Tumor-characteristic metabolites can be transformed into toxic substances under the catalysis of nanozymes to kill tumor cells. However, the therapeutic effects of nanozymes greatly depend on their catalytic activity, which displays a lot of differences in vitro and in vivo. Moreover, the complex tumor environment (low pH, high H2O2 and GSH concentration, hypoxia, etc.) plays an important role in affecting their catalytic activity. Besides, the uncontrollable catalysis of nanozymes may lead to the destruction of normal tissues. To solve these problems, researchers have exploited several imaging methods to monitor the reaction processes during catalysis, including optical imaging methods (fluorescence and chemiluminescence), photoacoustic imaging, and magnetic resonance imaging. In this review, we have summarized the development of tumor treatment using nanozymes in recent years, along with the current imaging tools to monitor the catalyzing activity of nanozymes. Representative examples have been elaborated on to show the current development of these imaging tools. We hope this review will provide some instructive perspectives on the development of nanozymes and promote the applications of imaging-guided tumor therapeutics.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Peróxido de Hidrogênio , Glucose Oxidase/química , Peroxidase , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
14.
Nano Lett ; 23(7): 2659-2668, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-36940420

RESUMO

The targeting of tumor metabolism as a novel strategy for cancer therapy has attracted tremendous attention. Herein, we develop a dual metabolism inhibitor, Zn-carnosine metallodrug network nanoparticles (Zn-Car MNs), which exhibits good Cu-depletion and Cu-responsive drug release, causing potent inhibition of both OXPHOS and glycolysis. Notably, Zn-Car MNs can decrease the activity of cytochrome c oxidase and the content of NAD+, so as to reduce ATP production in cancer cells. Thereby, energy deprivation, together with the depolarized mitochondrial membrane potential and increased oxidative stress, results in apoptosis of cancer cells. In result, Zn-Car MNs exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models. The efficacy and therapy of Zn-Car MNs suggest the possibility to overcome the drug resistance caused by metabolic reprogramming in tumors and has potential clinical relevance.


Assuntos
Neoplasias da Mama , Carnosina , Humanos , Feminino , Carnosina/metabolismo , Carnosina/farmacologia , Cobre/farmacologia , Glicólise , Zinco
15.
Angew Chem Int Ed Engl ; 61(48): e202206074, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36222012

RESUMO

Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T1 /T2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2 -mediated enhancement of key pathways of ferroptosis.


Assuntos
Ferroptose , Nanoestruturas , Humanos , Linhagem Celular Tumoral , Imageamento por Ressonância Magnética , Hipóxia
16.
Theranostics ; 12(14): 6207-6222, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36168615

RESUMO

Rationale: Ferroptosis drugs inducing cancer immunogenic cell death (ICD) have shown the potential of immunotherapy in vivo. However, the current ferroptosis drugs usually induce the insufficient immune response because of the low ROS generation efficiency. Methods: Herein, we design zinc-fluorouracil metallodrug networks (Zn-Fu MNs), by coordinating Zn and Fu via facile one-pot preparation, to inactivate mitochondrial electron transport for enhanced ROS production and immune activation. Results: Zn-Fu MNs can be responsive toward acidity and adenosine triphosphate (ATP) with the release of Fu and Zn2+, during which Zn2+ can induce mitochondrion disruption to produce ROS, resulting in ferroptosis of cancer cells and 5-Fu interferes with DNA synthesis in nuclei with 19F-MRI signal to be switched on for correlating drug release. With the synergistic effect of DNA damage and ferroptosis, the cancer cells are forced to promote ICD. Thereby, Zn-Fu MNs exhibit the excellent immune response without any other antigens loading. As a result, the infiltration of T cells within tumor and activation of immune cells in spleen have been greatly enhanced. Conclusions: Combined DNA damage and ferroptosis, Zn-Fu MNs induce the violent emission of tumor associated antigens within cancer cells which will sensitize naive dendritic cells and promote the activation and recruitment of cytotoxic T lymphocytes to exterminate cancer cells. Therefore, the obtained Zn-Fu MNs as ferroptosis inducers can effectively remodel immunosuppressive tumor microenvironment and activate antitumor immune reaction.


Assuntos
Ferroptose , Trifosfato de Adenosina , Linhagem Celular Tumoral , DNA , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Zinco
17.
Angew Chem Int Ed Engl ; 61(31): e202117229, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35460321

RESUMO

Ferroptosis exhibits potential to damage drug-resistant cancer cells. However, it is still restricted with the "off-target" toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment-triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high-field magnetic resonance imaging (MRI), which enables the real-time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T1 -/T2 -MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI-guided high-specificity ferroptosis therapy.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Ligas , Linhagem Celular Tumoral , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias/patologia , Microambiente Tumoral
18.
Adv Sci (Weinh) ; 7(18): 1903045, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32999824

RESUMO

SnS, is a promising anode material for lithium ion batteries (LIBs) and sodium ion batteries (SIBs), however, undergoes poor cyclic lifespan due to its huge volume changes and bad electroconductivity. Here, a modified CVD method is used to directly grow graphene-like carbon film on the surface of SnS nanosheet arrays which are supported by Co-, N-modified porous carbon fibers (CCF@SnS@G). In the strategy, the SnS nanosheet arrays confined into the integrated carbon matrix containing porous carbon fibers and graphene-like carbon film, perform a greatly improved electrochemical performance. In situ TEM experiments reveal that the vertical graphene-like carbon film can not only protect the SnS nanosheet from destruction well and enhance the conductivity, but also transforms SnS nanosheet into ultrafine nanoparticles to promote the electrochemical kinetics. Systematic electrochemical investigations exhibit that the CCF@SnS@G electrode delivers a stable reversible capacity of 529 mAh g-1 at a high current density of 5 A g-1 for LIBs and 541.4 mAh g-1 at 2 A g-1 for SIBs, suggesting its good potential for anode electrodes.

19.
Adv Sci (Weinh) ; 7(12): 1903674, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32596112

RESUMO

The hydrogen evolution reaction (HER) is a critical process in the electrolysis of water. Recently, much effort has been dedicated to developing low-cost, highly efficient, and stable electrocatalysts. Transition metal phosphides are investigated intensively due to their high electronic conductivity and optimized absorption energy of intermediates in acid electrolytes. However, the low stability of metal phosphide materials in air and during electrocatalytic processes causes a decay of performance and hinders the discovery of specific active sites. The HER in alkaline media is more intricate, which requires further delicate design due to the Volmer steps. In this work, phosphorus-modified monoclinic ß-CoMoO4 is developed as a low-cost, efficient, and stable HER electrocatalyst for the electrolysis of water in alkaline media. The optimized catalyst shows a small overpotential of 94 mV to reach a current density of 10 mA cm-2 for the HER with high stability in KOH electrolyte, and an overpotential of 197 mV to reach a current density of 100 mA cm-2. Combined computational and in situ spectroscopic techniques show P is present as a surface phosphate ion; that electron holes localize on the surface ions and both (P-O1-) and Co3+-OH- are prospective surface active sites for the HER.

20.
Dalton Trans ; 49(17): 5493-5502, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32266911

RESUMO

Heat therapy is a promising therapeutic modality for cancer treatment due to the minimum adverse effects of selective local hyperthermia; however, the low heating efficiency of heat therapy under safe conditions is an issue for its bioapplication. Here, we report the synthesis of water-dispersible sulfur doped iron oxides (SDIOs) with different phase structures and the exploration of the relationships between the different SDIOs and their induction heating capacities as a guideline to obtain a photo-magnetic hyperthermia agent. The agent exhibits good biocompatibility, excellent photothermal conversion efficiency (55.8%) and great T2 weighted magnetic resonance imaging (63.7 mM-1 s-1). Significantly, the SDIOs effectively eliminate tumours in a biologically safe AC magnetic field range (H·f = 4.3 < 5.0 × 106 kA m-1 s-1) and with 808 nm laser irradiation at a safe density of 0.33 W cm-2; also, they can be mostly metabolized from the body after one month. The work presented here adopts anion-doped iron oxides to dramatically improve photo-magnetic hyperthermia effects and may enable further exploration in thermotherapeutic research.


Assuntos
Compostos Férricos/química , Hipertermia Induzida/métodos , Imageamento por Ressonância Magnética , Fototerapia/métodos , Segurança , Enxofre/química , Animais , Células HeLa , Humanos , Camundongos
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