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1.
Nano Lett ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38912749

RESUMEN

Piezoelectric dynamic therapy (PzDT) is an effective method of tumor treatment by using piezoelectric polarization to generate reactive oxygen species. In this paper, two-dimensional Cu-doped BiOCl nanosheets with surface vacancies are produced by the photoetching strategy. Under ultrasound, a built-in electric field is generated to promote the electron and hole separation. The separated carriers achieve O2 reduction and GSH oxidation, inducing oxidative stress. The bandgap of BiOCl is narrowed by introducing surface oxygen vacancies, which act as charge traps and facilitate the electron and hole separation. Meanwhile, Cu doping induces chemodynamic therapy and depletes GSH via the transformation from Cu(II) to Cu(I). Both in vivo and in vitro results confirmed that oxidative stress can be enhanced by exogenous ultrasound stimulation, which can cause severe damage to tumor cells. This work emphasizes the efficient strategy of doping engineering and defect engineering for US-activated PzDT under exogenous stimulation.

2.
Mol Biol Rep ; 51(1): 679, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796668

RESUMEN

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5), a calcium-dependent cell membrane-binding protein, shows protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism of action. METHODS AND RESULTS: Different doses of AnxA5 were injected intravenously to treat bilateral renal IRI in SD rats. This model confirmed the protective effects of AnxA5 on kidney structure and function. In vitro, HK-2 cells were subjected to hypoxia for 12 h, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments demonstrated the mechanism of action of AnxA5 by measuring cellular activity and permeability. A comparison of the mutant AnxA5 protein M23 and the application of a calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure. CONCLUSIONS: Exogenous AnxA5 monomers prevented renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.


Asunto(s)
Anexina A5 , Riñón , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Ratas , Anexina A5/metabolismo , Anexina A5/farmacología , Humanos , Riñón/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Línea Celular , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Modelos Animales de Enfermedad
3.
J Am Chem Soc ; 145(17): 9488-9507, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-36998235

RESUMEN

Arming activatable mild-photothermal therapy (PTT) with the property of relieving tumor thermotolerance holds great promise for overcoming traditional mild PTT limitations such as thermoresistance, insufficient therapeutic effect, and off-target heating. Herein, a mitochondria-targeting, defect-engineered AFCT nanozyme with enhanced multi-enzymatic activity was elaborately designed as a tumor microenvironment (TME)-activatable phototheranostic agent to achieve remarkable anti-tumor therapy via "electron transport chain (ETC) interference and synergistic adjuvant therapy". Density functional theory calculations revealed that the synergistic effect among multi-enzyme active centers endows the AFCT nanozymes with excellent catalytic activity. In TME, open sources of H2O2 can be achieved by superoxide dismutase-mimicking AFCT nanozymes. In response to the dual stimuli of H2O2 and mild acidity, the peroxidase-mimicking activity of AFCT nanozymes not only catalyzes the accumulation of H2O2 to generate ·OH but also converts the loaded 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form with strong near-infrared absorption, specifically unlocking its photothermal and photoacoustic imaging properties. Intriguingly, the undesired thermoresistance of tumor cells can be greatly alleviated owing to the reduced expression of heat shock proteins enabled by NADH POD-mimicking AFCT-mediated NADH depletion and consequent restriction of ATP supply. Meanwhile, the accumulated ·OH can facilitate both apoptosis and ferroptosis in tumor cells, resulting in synergistic therapeutic outcomes in combination with TME-activated mild PTT.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Fototerapia/métodos , Peróxido de Hidrógeno , Transporte de Electrón , NAD , Nanopartículas/uso terapéutico , Neoplasias/terapia , Línea Celular Tumoral , Microambiente Tumoral
4.
J Dairy Sci ; 103(1): 117-127, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31704013

RESUMEN

Trait stability of Lactobacillus plantarum was studied following daily subculture over a 90-d period. Acid and bile tolerance, self-aggregation ability, cell hydrophobicity, pathogen inhibition activity, and cholesterol removal ability of cultures subcultured 30 (Lp30), 60 (Lp60), or 90 (Lp90) times were not significantly different from the original strain (Lp0). However, carbohydrate metabolism patterns did change; the Lp0 culture was unable to use d-sorbitol, α-methyl-d-mannose, and d-raffinose, whereas Lp30, Lp60, and Lp90 cultures could. Furthermore, gluconate and gentiobiose were fully used by the Lp0 culture but only poorly used by the Lp30, Lp60, and Lp90 cultures. Milk fermentation test confirmed that L. plantarum was unable to use lactose throughout laboratory evolution. Six non-synonymous mutations in genome of the Lp30, Lp60, and Lp90 cultures were identified by whole-genome sequencing, including mutant gene encoding the phosphoglycerate mutase, which is closely related to the transport and metabolism of carbohydrates. These mutations may play an important role in changes of carbohydrate metabolism patterns observed. Understanding the evolutionary characteristics of L. plantarum will help in development for food industry.


Asunto(s)
Proteínas Bacterianas/genética , Lactobacillus plantarum/genética , Probióticos , Secuenciación Completa del Genoma , Ácidos , Proteínas Bacterianas/metabolismo , Metabolismo de los Hidratos de Carbono , Fermentación , Laboratorios , Lactobacillus plantarum/fisiología , Mutación , Fenotipo , Fosfoglicerato Mutasa/genética
5.
Inorg Chem ; 57(16): 9988-9998, 2018 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-30070830

RESUMEN

The strategy of diagnosis-to-therapy to realize the integration of imaging and high antitumor efficiency has become the most promising method. Light-induced therapeutic technologies have drawn considerable interest. However, the limited penetration depth of UV/vis excitation and relatively low efficiency are the main obstacles for its further clinic application. For this concern, we presented a facile method to anchor ultrasmall ZnFe2O4 nanoparticles and upconversion luminescence nanoparticles (UCNPs) on graphene oxide (GO) nanosheets (GO/ZnFe2O4/UCNPs, abbreviated as GZUC). To solve the penetration question, here we introduced Tm3+-doped UCNPs to convert the high-penetrated near-infrared (NIR) light into UV/vis photons to activate the photodynamic process. In this system, the dual phototherapy from GO and ZnFe2O4 has been realized upon NIR laser irradiation. Combined with the photodynamic therapy (PDT) based on Fenton reaction that ZnFe2O4 nanoparticles react with excessive H2O2 in tumor microenvironment to produce toxic hydroxyl radicals (·OH), an excellent anticancer efficiency has been achieved. Furthermore, 4-fold imaging including upconversion luminescence (UCL), computed tomography (CT), magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) has been obtained due to its intrinsic properties, thereby successfully realizing diagnosis-monitored therapy. Our demonstration provided a feasible strategy to solve the main problems in current light-triggered theranostic.

6.
Int J Biol Sci ; 20(8): 2994-3007, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904008

RESUMEN

Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA treatment. This study investigated the role of Annexin A5 (AnxA5) within CEFFE in regulating macrophage polarization and protecting chondrocytes. In vitro experiments demonstrated that AnxA5 effectively inhibited M1 macrophage polarization by facilitating toll-like receptor (TLR) 4 internalization and lysosomal degradation through calcium-dependent endocytosis. This process decreased TLR4 expression, suppressed pro-inflammatory mediator release, and reduced the production of reactive oxygen species. Furthermore, AnxA5 displayed protective effects against chondrocyte necrosis and apoptosis. In vivo, studies revealed that intra-articular administration of AnxA5 ameliorated pain symptoms in a monosodium iodoacetate-induced osteoarthritis rat model. Histological analyses indicated a decrease in synovial inflammation and mitigation of cartilage damage following AnxA5 treatment. These results underscored the potential of AnxA5 as a therapeutic option for OA due to its capacity to regulate macrophage polarization and maintain chondrocyte viability. Further investigation into the specific mechanisms and clinical applications of AnxA5 may help improve the management of OA.


Asunto(s)
Anexina A5 , Condrocitos , Macrófagos , Osteoartritis , Ratas Sprague-Dawley , Animales , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Osteoartritis/inducido químicamente , Ratas , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Anexina A5/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Masculino , Receptor Toll-Like 4/metabolismo , Ratones , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos
7.
Sci Total Environ ; 939: 173414, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38796006

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs), widespread organic pollutants, significantly impact human health and environmental integrity. Recent approaches to ameliorate PAH-contaminated soils, particularly in cold environments, have been insufficient. This study investigates the use of immobilized low-temperature-resistant mixed microorganisms (LTRMM) for enhancing the degradation of PAHs in soils from coke plants and the Shenfu irrigation area. Our results demonstrate that treatment with immobilized mixed microorganisms (MC-HS) is more effective than treatments with free bacteria (H-S) and control (CK). Specifically, the degradation rates in the MC-HS1 treatment were 10.10 %-41.13 % higher than those in the coking plant soil treated with CK1 and H-S1. Similarly, in the Shenfu irrigation area soil, MC-HS2 showed improvements of 6.00 % to 52.56 % over CK2 and H-S2. A kinetic model was used to analyze the enhanced degradation capabilities, revealing that the half-life of PAHs under the immobilized mixed microorganism treatment (T3) was significantly shorter compared to the free bacteria (T2) and control treatments (T1). These findings suggest that employing immobilized LTRMM could significantly improve the remediation efficiency of PAH-contaminated soils in cold climates.


Asunto(s)
Biodegradación Ambiental , Frío , Hidrocarburos Policíclicos Aromáticos , Microbiología del Suelo , Contaminantes del Suelo , Hidrocarburos Policíclicos Aromáticos/análisis , Clima Frío , Suelo/química , China
8.
Regen Ther ; 27: 342-353, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38645281

RESUMEN

Background: One of the key obstacles to the healing of diabetic wound is the persistence of active inflammation. We previously demonstrated the potential of cell-free fat extract (CEFFE) to promote the healing of diabetic wounds, and annexin A5 (A5) is a crucial anti-inflammatory protein within CEFFE. This study aimed to evaluate the therapeutic potential of A5 in diabetic wounds. Methods: A5 was loaded into GelMA hydrogels and applied to skin wounds of diabetic mice in vivo. The diabetic wounds with the treatment of GelMA-A5 were observed for 14 days and evaluated by histological analysis. Accessment of inflammation regulation were conducted through anti-CD68 staining, anti-CD86 and anti-CD206 staining, and qRT-PCR of wound tissue. In presence of A5, macrophages stimulated by lipopolysaccharide (LPS) in vitro, and detected through qRT-PCR, flow cytometry, and immunocytofluorescence staining. Besides, epithelial cells were co-cultured with A5 for epithelialization regulation by CCK-8 assay and cell migration assay. Results: A5 could promote diabetic wound healing and regulate inflammations by promoting the transition of macrophages from M1 to M2 phenotype. In vitro experiments demonstrated that A5 exerted a significant effect on reducing pro-inflammatory factors and inhibiting the polarization of macrophages from M0 toward M1 phenotype. A5 significantly promoted the migration of epithelial cells. Conclusion: Annexin A5 has a significant impact on the regulation of macrophage inflammation and promotion of epithelialization.

9.
Aging Cell ; 23(4): e14157, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38558485

RESUMEN

A recently proposed principal law of lifespan (PLOSP) proposes to extend the whole human lifespan by elongating different life stages. As the preborn stage of a human being, gestation is the foundation for the healthy development of the human body. The antagonistic pleiotropy (AP) theory of aging states that there is a trade-off between early life fitness and late-life mortality. The question is whether slower development during the gestation period would be associated with a longer lifespan. Among all living creatures, the length of the gestation period is highly positively correlated to the length of the lifespan, although such a correlation is thought to be influenced by the body sizes of different species. While examining the relationship between lifespan length and body size within the same species, dogs exhibit a negative correlation between lifespans and body sizes, while there is no such correlation among domestic cats. For humans, most adverse gestational environments shorten the period of gestation, and their impacts are long-term. While many issues remain unsolved, various developmental features have been linked to the conditions during the gestation period. Given that the length of human pregnancies can vary randomly by as long as 5 weeks, it is worth investigating whether a slow steady healthy gestation over a longer period will be related to a longer and healthier lifespan. This article discusses the potential benefits, negative impacts, and challenges of the relative elongation of the gestation period.


Asunto(s)
Envejecimiento , Longevidad , Embarazo , Femenino , Humanos , Animales , Perros , Gatos , Tamaño Corporal
10.
Medicine (Baltimore) ; 103(6): e37229, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38335396

RESUMEN

Lung cancer is one of the most frequently diagnosed cancers in the world. There are an estimated 2.2 million new cases and 1.79 million deaths each year. Over the past 2 decades, our understanding of disease biology, the use of predictive biomarkers, and improvements in therapeutic approaches have made significant progress and transformed the outcomes of many patients. Treatment is determined by the subtype and stage of the cancer; however, the effect of personalized treatment remains unsatisfactory. The use of Chinese medicines has attracted increasing attention worldwide. Chinese medicine treatment of lung cancer has few side effects, which can effectively prolong the survival expectation of patients and improve their quality of life, and has attracted increasing attention. Based on the pathophysiological mechanism of lung cancer reported in modern medical research, this article explores the efficacy and safety of acupuncture combined with medicine in the treatment of lung cancer.


Asunto(s)
Terapia por Acupuntura , Acupuntura , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Calidad de Vida , Terapia por Acupuntura/efectos adversos , Terapia Combinada
11.
Anaesth Crit Care Pain Med ; 43(3): 101358, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38365169

RESUMEN

BACKGROUND: Most women with breast cancer are prone to postoperative sleep disturbances (POSD). Little is known about the differences between sevoflurane and propofol combined with dexmedetomidine on POSD in the same context. We investigated the effect of intra-operative sevoflurane or propofol combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep structures. METHODS: A monocentric, randomized-controlled, double-blind trial. Female patients undergoing radical surgery for breast cancer were randomly assigned to receive sevoflurane and placebo, sevoflurane and dexmedetomidine, propofol and placebo, or propofol and dexmedetomidine. Dexmedetomidine was administered at 1.0 µg kg-1 infusion 15 min before induction, then infused at 0.4 µg kg-1 h-1 until the surgical drain started to be placed. The primary outcome was the incidence of POSD within the postoperative first three days (defined as an Athens Insomnia Scale score ≥ 6 points on at least one day of postoperative first three days). The secondary outcome was the duration of sleep structures, collected from the Fitbit Charge 2® smart bracelet (Fitbit, Inc., San Francisco, CA, USA). RESULTS: There were 188 women analyzed with the modified intention-to-treat method. The incidences of POSD in the dexmedetomidine and placebo groups were similar (p = 0.649). In the sevoflurane sedation strategy, dexmedetomidine decreased nocturnal wakefulness on postoperative first day (p = 0.001). In the propofol sedation strategy, dexmedetomidine increased nocturnal deep sleep on postoperative first (p < 0.001) and third (p < 0.001) days. CONCLUSION: Intra-operative infusion of dexmedetomidine had no significant effect on POSD but decreased nocturnal wakefulness in the sevoflurane group and increased nocturnal deep sleep in the propofol group. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2300070136).


Asunto(s)
Neoplasias de la Mama , Dexmedetomidina , Hipnóticos y Sedantes , Complicaciones Posoperatorias , Propofol , Sevoflurano , Trastornos del Sueño-Vigilia , Humanos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Femenino , Método Doble Ciego , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Propofol/administración & dosificación , Propofol/efectos adversos , Sevoflurano/administración & dosificación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Hipnóticos y Sedantes/administración & dosificación , Trastornos del Sueño-Vigilia/etiología , Adulto , Anciano , Infusiones Intravenosas
12.
Biomed Pharmacother ; 167: 115513, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37741251

RESUMEN

Immune effector cells in the microenvironment tend to be depleted or remodeled, unable to perform normal functions, and even promote the malignant characterization of tumors, resulting in the formation of immunosuppressive microenvironments. The strategy of reversing immunosuppressive microenvironment has been widely used to enhance the tumor immunotherapy effect. Signal transducer and activator of transcription 3 (STAT3) was found to be a crucial regulator of immunosuppressive microenvironment formation and activation as well as a factor, stimulating tumor cell proliferation, survival, invasiveness and metastasis. Therefore, regulating the immune microenvironment by targeting the STAT3 oncogenic pathway might be a new cancer therapy strategy. This review discusses the pleiotropic effects of STAT3 on immune cell populations that are critical for tumorigenesis, and introduces the novel strategies targeting STAT3 oncogenic pathway for cancer immunotherapy. Lastly, we summarize the conventional drugs used in new STAT3-targeting anti-tumor applications.

13.
J Cancer ; 14(14): 2720-2725, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37779871

RESUMEN

Colorectal cancer is a common clinical malignant tumor of the digestive tract, and intestinal flora has played an important role in the development of colorectal cancer. Bifidobacteria, as one of the main dominant florae in intestinal tract, can inhibit the occurrence and development of colorectal cancer through various mechanisms. Recent studies have shown that traditional Chinese medicine can regulate the abundance of bifidobacteria in intestinal tract and exhibit anti-tumor effects on colorectal cancer. Detailed investigations have revealed that the mechanisms of bifidobacteria in the treatment of colorectal cancer involve three aspects: the production of short-chain fatty acids, the regulation of the body's immunity, and the regulation of cell apoptosis and differentiation. In this review, we provide an updated summary of recent advances in our understanding of the mechanisms by which traditional Chinese medicine regulate intestinal flora to inhibit colorectal cancer development and metastasis.

14.
Drug Des Devel Ther ; 17: 839-849, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969707

RESUMEN

Purpose: This study was designed to investigate the effects of different doses of butorphanol on postoperative shivering and quality of recovery in elderly patients. Patients and Methods: A total of 147 elderly patients (aged 60 or older) scheduled for elective transurethral resection of the prostate were enrolled in the current study. Patients were randomly and evenly assigned into four groups: Group C (0.9% normal saline), Group B1 (butorphanol 0.01 mg/kg), Group B2 (butorphanol 0.02 mg/kg) and Group B3 (butorphanol 0.03 mg/kg). All drugs were diluted to 5mL and injected intravenously slowly 5 min before induction of anesthesia. The primary outcome measure was the incidence of postoperative shivering in the post-anesthesia care unit. Quality of Recovery-40 (QoR-40) scores were assessed on postoperative day (POD) 1, 2 and 3. Perioperative core and skin temperature, extubation time and adverse events were also recorded. Results: Patients among the four groups had comparable baseline characteristics. Compared with Group C, the incidence of shivering was significantly lower in Group B2 and B3 (P = 0.006 and P = 0.005, respectively). The QoR-40 scores on POD1 were significantly higher in all butorphanol groups than that in Group C (P < 0.0083). In Group B2 and B3, patients experienced lower pain intensity (P < 0.001). In addition, the incidence of catheter-related bladder discomfort (CRBD) was lower in all butorphanol groups than in Group C (P < 0.0083). Conclusion: Butorphanol 0.02 or 0.03 mg/kg could effectively prevent the occurrence of postoperative shivering in elderly patients scheduled for transurethral resection of the prostate, provided effective postoperative recovery and postoperative analgesia.


Asunto(s)
Anestesia , Resección Transuretral de la Próstata , Masculino , Anciano , Humanos , Butorfanol , Tiritona , Periodo Posoperatorio , Método Doble Ciego , Dolor Postoperatorio/tratamiento farmacológico
15.
Sci Adv ; 9(44): eadi9980, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37910608

RESUMEN

Thermoelectric therapy has emerged as a promising treatment strategy for oncology, but it is still limited by the low thermoelectric catalytic efficiency at human body temperature and the inevitable tumor thermotolerance. We present a photothermoelectric therapy (PTET) strategy based on triphenylphosphine-functionalized Cu3VS4 nanoparticles (CVS NPs) with high copper ionic mobility at room temperature. Under near-infrared laser irradiation, CVS NPs not only generate hyperthermia to ablate tumor cells but also catalytically yield superoxide radicals and induce endogenous NADH oxidation through the Seebeck effect. Notably, CVS NPs can accumulate inside mitochondria and deplete NADH, reducing ATP synthesis by competitively inhibiting the function of complex I, thereby down-regulating the expression of heat shock proteins to relieve tumor thermotolerance. Both in vitro and in vivo results show notable tumor suppression efficacy, indicating that the concept of integrating PTET and mitochondrial metabolism modulation is highly feasible and offers a translational promise for realizing precise and efficient cancer treatment.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Cobre/química , NAD , Fototerapia/métodos , Neoplasias/terapia , Neoplasias/patología , Nanopartículas/química , Línea Celular Tumoral
16.
ACS Nano ; 17(20): 20402-20423, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37811650

RESUMEN

The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a trimetallic alloy nanozyme AuCuPt-PpIX (ACPP), which mimics up to five naturally occurring enzymes: glucose oxidase (GOD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx). Facilitated by these enzyme-mimicking traits, the constructed ACPP nanozymes can not only disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions but also achieve cyclic regeneration of the relevant enzyme substrates. Density functional theory (DFT) calculations have theoretically explained the synergistic effect of multimetallic doping and the possible mechanism of enzymatic catalysis. The doped Cu and Pt sites are conducive to the adsorption, activation, and dissociation of reactant molecules, whereas the Au sites are conducive to desorption, which significantly improves catalytic efficiency via a synergistic effect. Additionally, ACPP nanozymes can improve the effect of protoporphyrin (PpIX)-enabled sonodynamic therapy (SDT) by alleviating hypoxia and initiating ferroptosis by inducing lipid peroxidation (LPO) and inhibiting GPX4 activity, thus achieving multimodal synergistic therapy. This study presents a typical paradigm to enable the use of multimetallic alloy nanozymes for the treatment of tumor cells with self-adaptive properties.


Asunto(s)
Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Peroxidasa , Peroxidasas , Oxidación-Reducción , Glucosa Oxidasa , Catálisis
17.
ACS Appl Mater Interfaces ; 14(19): 21787-21799, 2022 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-35506665

RESUMEN

As the least toxic heavy metal, monoelemental bismuth nanomaterials with several superiorities are the ideal theranostic agents. However, bismuth nanoparticles are easily oxidized by oxygen in air or media, limiting their clinical application. In contrast, the oxidization of Bi0 to Bi3+ can activate the chemodynamic therapy (CDT) by transferring endogenous H2O2 into •OH. Herein, a well-designed Bi-DMSNs@PCM nanosystem was prepared via in situ growth of Bi nanodots and a coating of phase-change material (PCM) on the surface of dendritic mesoporous silica nanoparticles (DMSNs). The coated PCM protects the Bi nanodots from oxidation by keeping them in the Bi0 state for more than 15 d. When irradiated using the near infrared-II (NIR-II) laser with a low power density (0.5 W/cm2), the heat generated from the Bi nanodots melts the PCM shell to trigger CDT through a Fenton-like reaction, accompanied by heat-induced photothermal therapy (PTT). Notably, the CDT can also compensate for the reduced PTT effect caused by the oxidation of Bi nanodots, and a satisfactory treatment effect is realized. Additionally, photoacoustic and computed tomography imaging properties were obtained. Our strategy transfers the detrimental self-oxidation of bismuth to a beneficial therapeutic mode, enhancing the potential of Bi for clinical use.


Asunto(s)
Bismuto , Nanopartículas , Línea Celular Tumoral , Peróxido de Hidrógeno , Terapia Fototérmica , Nanomedicina Teranóstica/métodos
18.
J Colloid Interface Sci ; 623: 787-798, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35636288

RESUMEN

Although nanocatalytic therapy has become an emerging strategy for tumor treatment, the therapeutic effects of reactive oxygen species (ROS)-mediated treatment are still seriously limited by the inherent flaws of the enzymatic activities and the specific physicochemical properties of the tumor microenvironment (TME). Herein, we report an ultrasmall bimetallic oxide nanozyme (CuFe2O4@PEG, CFOs) for programmable multienzyme-like activities-primed combined therapy. Under the acidic condition, abundant highly toxic ROS can be generated through the peroxidase activity of CFOs with overexpressed hydrogen peroxide (H2O2) in the tumor. High metal ion utilization of bimetallic oxide nanozymes is related to the size effect and topological structure. Furthermore, glutathione peroxidase activity-initiated depletion of GSH disrupts the intracellular antioxidant defense system and further amplifies the oxidative stress in turn. Subsequently, oxygen generation originating from the catalase activity of CFOs relieves tumor hypoxia and achieves exceptional TME-customized therapeutic effects. Notably, the high photothermal effect (η = 41.12%) of CFOs in the second near-infrared biological windows leads to the combinational inhibition of tumor growth. In summary, this report provides a paradigm for the rational design of TME-responsive and ROS-mediated nanocatalytic treatment, which is promising for achieving superior therapeutic efficiency.


Asunto(s)
Peróxido de Hidrógeno , Neoplasias , Antioxidantes , Línea Celular Tumoral , Glutatión/metabolismo , Humanos , Peróxido de Hidrógeno/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Estrés Oxidativo , Óxidos/farmacología , Especies Reactivas de Oxígeno , Microambiente Tumoral
19.
Drug Des Devel Ther ; 16: 1171-1181, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35496368

RESUMEN

Purpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia. Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded. Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P <0.001) in group L (165.5±3.8 vs 173.7±4.7) than those in group C (155.6±4.0 vs 163.2±4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P <0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P <0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality. Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.


Asunto(s)
Lidocaína , Neoplasias Supratentoriales , Adulto , Anestésicos Locales , Humanos , Interleucina-6 , Lidocaína/uso terapéutico , Dolor , Solución Salina , Neoplasias Supratentoriales/tratamiento farmacológico , Neoplasias Supratentoriales/cirugía , Factor de Necrosis Tumoral alfa
20.
Nanoscale ; 14(2): 361-372, 2022 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-34878482

RESUMEN

The construction of nanoplatforms with combined photothermal properties and cascading enzymatic activities has become an active area of anticancer research. However, the overheating of photothermal therapy (PTT) and the specific properties of tumor microenvironment (TME) greatly impaired the therapeutic efficiency. Herein, we rationally fabricated a virus-like SiOx/CeO2/VOx (SCV) nanoplatform for 1064 nm near-infrared (NIR) triggered mild-temperature PTT and nanozyme catalytic therapy. Firstly, the virus-like shape of SiOx/CeO2/VOx made it favorable for cell adhesion and improved its phagocytosis in cells, and the SCV generated an effective PTT effect upon 1064 nm laser irradiation. Particularly, the produced VO2+ in TME could be used as a heat shock protein inhibitor to inhibit the expression of heat shock protein 60 (HSP60) to enhance the PTT efficiency. Moreover, the SCV nanozyme exhibited obvious peroxidase-mimic (POD) catalytic activity, which could generate highly toxic free radical ions (˙OH) under acidic conditions. The mild-temperature heat and ˙OH produced by enzymatic catalysis effectively blocked the tumor growth, as verified firmly by in vitro and in vivo tests. Our designed virus-like SCV nanozyme with POD mimic enzyme activity and a mild photothermal effect may provide a new way of thinking about the combination therapy model.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Catálisis , Terapia Fototérmica , Temperatura , Microambiente Tumoral
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