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1.
Mol Cancer ; 22(1): 124, 2023 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-37543587

RESUMEN

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations. METHODS: This phase 2, single-arm, multicenter trial (ClinicalTrials.gov NCT03736837) was performed at five hospitals in China from December 2018 to November 2020. Non-squamous NSCLC cases with EGFR-sensitizing mutations were treated with anlotinib and icotinib. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. RESULTS: Sixty participants were enrolled, including 31 (52%) and 29 (48%) with concurrent mutations and pathogenic concurrent mutations, respectively. The median follow-up was 26.9 (range, 15.0-38.9) months. ORR and DCR were 68.5% and 98.2%, respectively. Median PFS was 15.1 (95%CI: 12.6-17.6) months which met the primary endpoint, median DoR was 13.5 (95%CI: 10.0-17.1) months, and median OS was 30.0 (95%CI: 25.5-34.5) months. Median PFS and OS in patients with pathogenic concurrent mutations were 15.6 (95%CI: 12.5-18.7) months and not reached (95%CI: 17.46 months to not reached), respectively. All patients experienced TRAEs, including 26 (43%) and 1 (1.7%) who had grade ≥ 3 and serious treatment-related adverse events (TRAEs). CONCLUSIONS: Anlotinib combined with icotinib was effective and well-tolerated as a first-line treatment option for EGFR mutation-positive advanced NSCLC with or without concurrent mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03736837.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Estudios Prospectivos , Receptores ErbB/genética , Mutación
2.
Clin Lab ; 66(9)2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32902217

RESUMEN

BACKGROUND: Small cell lung cancer is an aggressive form of lung cancer with poor prognosis. Combined serum biomarkers may give us more information and predictive value. METHODS: We retrospectively analyzed data and samples collected from 120 small cell lung cancer patients who had undergone surgery in Tianjin Medical University Cancer Institute and Hospital between June 2014 and November 2016. Correlations between serum biomarker levels and survival parameters were analyzed and prognostic factors were identified. RESULTS: By univariate analysis, limited disease (p < 0.001), more than 4 cycles of first line chemotherapy (p = 0.002), thoracic irradiation (p < 0.001), PCI (p = 0.013)), higher SCCA level (p = 0.058), and normal LDH level (p = 0.027) were significantly correlated with a good PFS. By multivariate analysis, clinical stage, number of chemotherapy cycles, thoracic irradiation, PCI, and SCCA level were independent prognostic factors for PFS. Higher ProGRP or NSE level with higher LDH, higher NSE with higher D-dimer had poor prognostic index. CONCLUSIONS: We observed that NSE, CEA, and CYFRA 21-1 were closely associated with tumor burden. The combination of NSE and ProGRP with LDH and D-dimer worked as prognostic factors for tumor progression in SCLC patients.


Asunto(s)
Neoplasias Pulmonares , Intervención Coronaria Percutánea , Carcinoma Pulmonar de Células Pequeñas , Antígenos de Neoplasias , Biomarcadores de Tumor , Humanos , Queratina-19 , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Fosfopiruvato Hidratasa , Pronóstico , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/terapia
3.
Med Sci Monit ; 25: 675-690, 2019 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-30673691

RESUMEN

BACKGROUND An extensive body of research reveals the clinical value of serum tumor markers in lung cancer patients, including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), cytokeratin-19 fragments (Cyfra21-1), and neuron-specific enolase (NSE), but little is known about the clinical properties of these serum tumor markers in anaplastic lymphoma kinase (ALK)-positive lung cancer patients. MATERIAL AND METHODS We retrospectively analyzed 54 patients harboring ALK rearrangements and 520 patients without ALK rearrangements, and all these patients were treated exclusively by surgery between 2011 and 2016. RESULTS NSE level (P=0.007 for OS) was identified as an independent prognostic factor among patients with resected ALK-positive adenocarcinoma of the lung. CONCLUSIONS A high level of NSE is associated with worse outcome among resected lung adenocarcinoma patients harboring ALK rearrangements.


Asunto(s)
Adenocarcinoma del Pulmón/metabolismo , Quinasa de Linfoma Anaplásico/genética , Fosfopiruvato Hidratasa/metabolismo , Adenocarcinoma/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/metabolismo , Antígenos de Neoplasias , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , China , Femenino , Humanos , Queratina-19 , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/fisiología , Pronóstico , Estudios Retrospectivos
4.
Adv Healthc Mater ; 13(22): e2400746, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38683107

RESUMEN

Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio-chemical features, such as high surface-to-volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio-chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti-inflammation, and anti-aging. In addition, the catalytic activity of nanozymes can specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, a systematic and comprehensive review of the challenges and recent development of CNPs for biomedical applications is presented from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, the biosafety issue of applying biodegradable and non-biodegradable nanozymes and future perspectives are critically discussed to guide a promising direction in developing span-new nanozymes and more intelligent strategies for overcoming the current clinical limitations.


Asunto(s)
Nanopartículas , Humanos , Catálisis , Nanopartículas/química , Animales , Especies Reactivas de Oxígeno/metabolismo , Técnicas Biosensibles/métodos
5.
ACS Appl Mater Interfaces ; 16(34): 45356-45370, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39143699

RESUMEN

This study emphasizes the innovative application of FePt and Cu core-shell nanostructures with increased lattice microstrain, coupled with Au single-atom catalysis, in significantly enhancing •OH generation for catalytic tumor therapy. The combination of core-shell with increased lattice microstrain and single-atom structures introduces an unexpected boost in hydroxyl radical (•OH) production, representing a pivotal advancement in strategies for enhancing reactive oxygen species. The creation of a core-shell structure, FePt@Cu, showcases a synergistic effect in •OH generation that surpasses the combined effects of FePt and Cu individually. Incorporating atomic Au with FePt@Cu/Au further enhances •OH production. Both FePt@Cu and FePt@Cu/Au structures boost the O2 → H2O2 → •OH reaction pathway and catalyze Fenton-like reactions. This enhancement is underpinned by DFT theoretical calculations revealing a reduced O2 adsorption energy and energy barrier, facilitated by lattice mismatch and the unique catalytic activity of single-atom Au. Notably, the FePt@Cu/Au structure demonstrates remarkable efficacy in tumor suppression and exhibits biodegradable properties, allowing for rapid excretion from the body. This dual attribute underscores its potential as a highly effective and safe cancer therapeutic agent.


Asunto(s)
Cobre , Oro , Catálisis , Oro/química , Cobre/química , Humanos , Animales , Ratones , Radical Hidroxilo/química , Antineoplásicos/química , Antineoplásicos/farmacología , Platino (Metal)/química , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/química , Nanoestructuras/química , Hierro/química , Línea Celular Tumoral , Peróxido de Hidrógeno/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Nanopartículas del Metal/química
6.
Adv Mater ; 36(30): e2404120, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38727702

RESUMEN

This study innovatively addresses challenges in enhancing upconversion efficiency in lanthanide-based nanoparticles (UCNPs) by exploiting Shewanella oneidensis MR-1, a microorganism capable of extracellular electron transfer. Electroactive membranes, rich in c-type cytochromes, are extracted from bacteria and integrated into membrane-integrated liposomes (MILs), encapsulating core-shelled UCNPs with an optically inactive shell, forming UCNP@MIL constructs. The electroactive membrane, tailored to donate electrons through the inert shell, independently boosts upconversion emission under near-infrared excitation (980 or 1550 nm), bypassing ligand-sensitized UCNPs. The optically inactive shell restricts energy migration, emphasizing electroactive membrane electron donation. Density functional theory calculations elucidate efficient electron transfer due to the electroactive membrane hemes' highest occupied molecular orbital being higher than the valence band maximum of the optically inactive shell, crucial for enhancing energy transfer to emitter ions. The introduction of a SiO2 insulator coating diminishes light enhancement, underscoring the importance of unimpeded electron transfer. Luminescence enhancement remains resilient to variations in emitter or sensitizing ions, highlighting the robustness of the electron transfer-induced phenomenon. However, altering the inert shell material diminishes enhancement, emphasizing the role of electron transfer. This methodology holds significant promise for diverse biological applications. UCNP@MIL offers an advantage in cellular uptake, which proves beneficial for cell imaging.


Asunto(s)
Electrones , Shewanella , Shewanella/metabolismo , Transporte de Electrón , Liposomas/química , Nanopartículas/química , Elementos de la Serie de los Lantanoides/química , Teoría Funcional de la Densidad
7.
ACS Appl Mater Interfaces ; 16(9): 12018-12032, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38394675

RESUMEN

Nonantibiotic approaches must be developed to kill pathogenic bacteria and ensure that clinicians have a means to treat wounds that are infected by multidrug-resistant bacteria. This study prepared matchstick-like Ag2S-ZnS heteronanostructures (HNSs). Their hydrophobic surfactants were then replaced with hydrophilic poly(ethylene glycol) (PEG) and thioglycolic acid (TGA) through the ligand exchange method, and this was followed by ascorbic acid (AA) conjugation with TGA through esterification, yielding well-dispersed PEGylated Ag2S-ZnS@TGA-AA HNSs. The ZnS component of the HNSs has innate semiconductivity, enabling the generation of electron-hole pairs upon irradiation with a light of wavelength 320 nm. These separate charges can react with oxygen and water around the HNSs to produce reactive oxygen species. Moreover, some holes can oxidize the surface-grafted AA to produce protons, decreasing the local pH and resulting in the corrosion of Ag2S, which releases silver ions. In evaluation tests, the PEGylated Ag2S-ZnS@TGA-AA had synergistic antibacterial ability and inhibited Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Additionally, MRSA-infected wounds treated with a single dose of PEGylated Ag2S-ZnS@TGA-AA HNSs under light exposure healed significantly more quickly than those not treated, a result attributable to the HNSs' excellent antibacterial and Bohr effects.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infección de Heridas , Humanos , Antibacterianos/farmacología , Cicatrización de Heridas , Polietilenglicoles/farmacología , Concentración de Iones de Hidrógeno
8.
Cancer Sci ; 104(4): 445-52, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23298271

RESUMEN

The current criteria for evaluating antiangiogenic efficacy is insufficient as tumor shrinkage occurs after blood perfusion decreases. Tumor blood volume (BV) in computed tomography perfusion imaging and circulating endothelial cells (CEC) might predict the status of angiogenesis. The present study aimed to validate their representation as feasible predictors in non-small-cell lung carcinoma (NSCLC). A total of 74 patients was categorized randomly into two arms undergoing regimens of vinorelbine and cisplatin (Navelbine and platinum [NP]) with rh-endostatin or single NP. The response rate, perfusion imaging indexes and activated CEC (aCEC) during treatment were recorded. Progression-free survival (PFS) was determined through follow up. Correlations among the above indicators, response and PFS were analyzed: aCEC increased significantly in cases of progressive disease after single NP chemotherapy (P = 0.024). Tumor BV decreased significantly in cases with a clinical benefit in the combined arm (P = 0.026), whereas inverse correlations existed between ∆aCEC (post-therapeutic value minus the pre-therapeutic value) and PFS (P = 0.005) and between ∆BV and PFS (P = 0.044); a positive correlation existed between ∆aCEC and ∆BV. Therefore, both aCEC and tumor BV can serve as predictors, and detection of both indicators can help evaluate the chemo-antiangiogenic efficacy in NSCLC more accurately.


Asunto(s)
Volumen Sanguíneo , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Células Endoteliales/patología , Neoplasias Pulmonares/irrigación sanguínea , Vinblastina/análogos & derivados , Adulto , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Endostatinas/administración & dosificación , Femenino , Predicción , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Vinblastina/administración & dosificación , Vinorelbina
9.
EBioMedicine ; 91: 104564, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37094467

RESUMEN

BACKGROUND: Intratumor heterogeneity (ITH) has been associated with poor prognosis in advanced non-small cell cancer (NSCLC) patients receiving immune checkpoint blockade (ICB) therapies. However, there is currently no evidence supporting an ITH metric as a predictor of clinical benefit from ICB. The unique advantages of blood make it a promising material for ITH estimation and relevant applications. This study aims to develop and validate a blood-based ITH index for predicting ICB response. METHODS: NSCLC patients from the OAK and POPLAR clinical trials were used as the training cohorts for algorithm development. Survival analyses with overall survival (OS) and progression-free survival (PFS) as endpoints were performed to assess clinical response. The predictive value of bITH was subsequently validated with an independent cohort of 42 NSCLC patients treated with PD-1 blockade. FINDINGS: bITH was significantly associated with the differential OS and PFS elicited by atezolizumab vs. docetaxel in both univariable and multivariable analyses in the OAK patients, suggesting bITH as an independent predictor for response to ICB. Moreover, compared with blood tumor mutation burden (bTMB), bITH enabled greater OS segregation and comparable PFS segregation, and obtained a predictive role regardless of bTMB status. Moreover, the association between bITH and PFS was validated with an independent cohort. INTERPRETATION: Patients with low blood-based ITH metric manifest significant OS and PFS benefit from immunotherapy versus chemotherapy. Future research is awaited to corroborate our findings and to enrich the clinical utility of ITH. FUNDING: This study was supported by the National Natural Science Foundation of China (Nos. 81972718 and 81572321), the Natural Scientific Foundation of Zhejiang Province, China (No. LY19H160007), the Science and Technology Program for Health and Medicine in Zhejiang Province, China (No. 2021KY541), the Scientific Research Project, Science and Technology Department of Sichuan Province (No. 21YYJC1616), the Scientific Research Project, Sichuan Medical Association (No. S20002), Wu Jieping Medical Foundation (No. 320.6750), and 2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (No. 2022-L023).


Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Supervivencia sin Progresión
10.
Nat Commun ; 14(1): 4709, 2023 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-37543632

RESUMEN

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.


Asunto(s)
Nanopartículas , Neoplasias , Masculino , Animales , Ratones , Dominio Catalítico , Peróxido de Hidrógeno , Catálisis , Agua , Línea Celular Tumoral
11.
Front Med (Lausanne) ; 9: 960316, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36186776

RESUMEN

Background: Portal hypertension monitoring is important throughout the natural course of cirrhosis. Hepatic venous pressure gradient (HVPG), regarded as the golden standard, is limited by invasiveness and technical difficulties. Portal hypertension is increasingly being assessed non-invasively, and hematological indices, imaging data, and statistical or computational models are studied to surrogate HVPG. This paper discusses the existing non-invasive methods based on measurement principles and reviews the methodological developments in the last 20 years. Methods: First, we used VOSviewer to learn the architecture of this field. The publications about the non-invasive assessment of portal hypertension were retrieved from the Web of Science Core Collection (WoSCC). VOSviewer 1.6.17.0 was used to analyze and visualize these publications, including the annual trend, the study hotspots, the significant articles, authors, journals, and organizations in this field. Next, according to the cluster analysis result of the keywords, we further retrieved and classified the related studies to discuss. Results: A total of 1,088 articles or review articles about our topic were retrieved from WoSCC. From 2000 to 2022, the number of publications is generally growing. "World Journal of Gastroenterology" published the most articles (n = 43), while "Journal of Hepatology" had the highest citations. "Liver fibrosis" published in 2005 was the most influential manuscript. Among the 20,558 cited references of 1,088 retrieved manuscripts, the most cited was a study on liver stiffness measurement from 2007. The highest-yielding country was the United States, followed by China and Italy. "Berzigotti, Annalisa" was the most prolific author and had the most cooperation partners. Four study directions emerged from the keyword clustering: (1) the evaluation based on fibrosis; (2) the evaluation based on hemodynamic factors; (3) the evaluation through elastography; and (4) the evaluation of variceal bleeding. Conclusion: The non-invasive assessment of portal hypertension is mainly based on two principles: fibrosis and hemodynamics. Liver fibrosis is the major initiator of cirrhotic PH, while hemodynamic factors reflect secondary alteration of splanchnic blood flow. Blood tests, US (including DUS and CEUS), CT, and magnetic resonance imaging (MRI) support the non-invasive assessment of PH by providing both hemodynamic and fibrotic information. Elastography, mainly USE, is the most important method of PH monitoring.

12.
ACS Appl Mater Interfaces ; 14(21): 24144-24159, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35579575

RESUMEN

Lung cancer is considered among the deadliest cancers with a poor prognosis. Au@PG nanoparticles (NPs) are gold (Au)-based NPs featuring a polyaniline-based glyco structure (PG) generated from the polymerization of ortho-nitrophenyl-ß-d-galactopyranoside (ONPG) with promising M1 macrophage polarization activity, resulting in tumor remodeling and from a cold to a hot microenvironment, which promotes the cytotoxic T cell response and tumor inhibition. The combination of Au@PG NPs and anti-programmed cell death protein 1 (PD-1) therapy improved tumor inhibition and immunosuppression, accompanied by the secretion of immunogenic cytokines. A one-pot synthetic method was developed to achieve glyco-condensation during the formation of Au@PG NPs, which induced macrophage polarization more efficiently than Au@glucose, Au@mannose, and Au@galactose NPs. The switch from M2 to M1 macrophages was dependent on NP size, with smaller Au@PG NPs performing better than larger ones, with effectiveness ranked as follows: 32.2 nm ≈ 29.8 nm < 26.4 nm < 18.3 nm. Cellular uptake by endocytosis induced size-dependent endoplasmic reticulum (ER) stress, which resulted in the activation of spleen tyrosine kinase (SYK), leading to immune modulations and macrophage polarization. Our results suggested the promising potential of Au@PG NPs in lung cancer immunotherapy.


Asunto(s)
Neoplasias Pulmonares , Nanopartículas del Metal , Nanopartículas , Compuestos de Anilina , Oro/química , Humanos , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Nanopartículas/química , Microambiente Tumoral
13.
Nat Commun ; 13(1): 7772, 2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36522345

RESUMEN

Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl4 allows for the fabrication of different atomic ratios of AuxCuy. X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au0.02Cu0.98 composition reveals the enhanced •OH generation following O2 → H2O2 → •OH. The degradable Au0.02Cu0.98 released Cu+ and Cu2+ resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au0.02Cu0.98 for O2 → H2O2 → •OH as well. Instead of using endogenous H2O2, H2O2 can be sourced from the O2 in the air through the use of nanocubes. Notably, the Au0.02Cu0.98 structure is degradable and renal-clearable.


Asunto(s)
Cobre , Oxígeno , Femenino , Ratones , Animales , Cobre/química , Oxígeno/química , Peróxido de Hidrógeno/química , Oxidación-Reducción , Oro
14.
ACS Appl Mater Interfaces ; 14(11): 13056-13069, 2022 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-35253424

RESUMEN

Ineffective site-specific delivery has seriously impeded the efficacy of nanoparticle-based drugs to a disease site. Here, we report the preparation of three different shapes (sphere, scroll, and oblate) to systematically evaluate the impact of the marginative delivery on the efficacy of magnetic resonance (MR) imaging-guided X-ray irradiation at a low dose of 1 Gy. In addition to the shape effect, the therapeutic efficacy is investigated for the first time to be strongly related to the structure effect that is associated with the chemical activity. The enhanced particle-vessel wall interaction of both the flat scroll and oblate following margination dynamics leads to greater accumulation in the lungs, resulting in superior performance over the sphere against lung tumor growth and suppression of lung metastasis. Furthermore, the impact of the structural discrepancy in nanoparticles on therapeutic efficacy is considered. The tetragonal oblate reveals that the feasibility of the charge-transfer process outperforms the orthorhombic scroll and cubic sphere to suppress tumors. Finally, surface area is also a crucial factor affecting the efficacy of X-ray treatments from the as-prepared particles.


Asunto(s)
Neoplasias Pulmonares , Nanopartículas , Terapia por Rayos X , Humanos , Pulmón , Neoplasias Pulmonares/diagnóstico por imagen , Imagen por Resonancia Magnética , Nanopartículas/química , Nanopartículas/uso terapéutico
15.
ACS Nano ; 15(5): 9084-9100, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-33974409

RESUMEN

Pancreatic cancer is among the leading causes of cancer-related death and remains a formidable therapeutic challenge. To date, surgical resection and chemotherapy have been the standards of care. Methotrexate (MTX), which is recognized as a refractory drug for pancreatic cells, was conjugated to the surface of LiYF4:Ce3+ nanoparticles (NP-MTX) through a photocleavable linker molecule. When LiYF4:Ce3+ NPs are stimulated by X-rays, they emit light, which induces the photocleavage of the photolabile linker molecule to release MTX. MTX can target pancreatic tumors, which overexpress folic acid (FA) receptors and are internalized into the cell through receptor-mediated endocytosis. The synergistic effect of the NP-MTX treatment initiated by X-ray irradiation occurs due to the combination of nanoparticle sensitization and the radiosensitizing chemotherapy of the photocleaved MTX molecule. This dual sensitization effect mediated by NP-MTX enabled 40% dose enhancement, which corresponded with an increase in the generation of cytotoxic cellular reactive oxygen species (ROS) and enhanced S phase arrest within the cell cycle. The delivery of an ultralow radiation dose of 0.1 Gy resulted in the photocleavage of MTX from NP-MTX, and this strategy demonstrated in vivo efficacy against AsPC-1 and PANC-1 xenografted pancreatic tumors.


Asunto(s)
Nanopartículas , Neoplasias Pancreáticas , Puntos de Control del Ciclo Celular , Sistemas de Liberación de Medicamentos , Humanos , Metotrexato , Neoplasias Pancreáticas/tratamiento farmacológico , Rayos X
16.
J Mater Chem B ; 9(3): 694-709, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33367451

RESUMEN

The second near-infrared biological window b (NIR-IIb, 1500-1700 nm) is recently considered as the promising region for deeper tissue penetration. Herein, a nanocarrier for 1550 nm light-responsive dual-photodynamic therapy (PDT) is developed to efficiently boost singlet oxygen (1O2) generation. The dual-photosensitizers (PSs), rose bengal (RB) and chlorin e6 (Ce6), are carried by the silica-coated core-shell LiYbF4:Er@LiGdF4 upconversion nanoparticles (UCNPs), forming UCNP/RB,Ce6. Following 1550 nm laser irradiation, the upconversion emission of UCNP/RB,Ce6 in both green (∼550 nm) and red (∼670 nm) colors is fully utilized to activate RB and Ce6, respectively. The simultaneous triggering of dual-PS generates an abundant amount of 1O2 resulting in boosted PDT efficacy. This dual-PDT nanocarrier presents an enhanced anticancer effect under single dose treatment in comparison with the single-PS ones from in vitro and in vivo treatments. The marriage between the boosted dual-PDT and 1550 nm light excitation is anticipated to provide a new avenue for non-invasive therapy.


Asunto(s)
Antineoplásicos/farmacología , Nanopartículas/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Rayos Infrarrojos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Estructura Molecular , Nanopartículas/química , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Imagen Óptica , Neoplasias Pancreáticas/patología , Tamaño de la Partícula , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Propiedades de Superficie , Células Tumorales Cultivadas
17.
Cancer Lett ; 503: 197-212, 2021 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-33493586

RESUMEN

Patient mortality rates have remained stubbornly high for the past decades in small cell lung cancer (SCLC) because of having no standard targeted therapies with confirmed advantages at present. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models but have had unsatisfactory clinical results in SCLC. By RNA-seq and isobaric tags for relative and absolute quantification (ITRAQ), we revealed that PARP1 inhibition led to the relocalization of forkhead box-O3a (FOXO3a) from nuclear to cytoplasm. By performing co-Immunoprecipitation (co-IP) and CRISPR-Cas9-mediated knockout plasmid we showed that FOXO3a was subject to exportin 1 (XPO1)-dependent nuclear export. We demonstrated the effects of the PARP inhibitor BMN673 on apoptosis and DNA damage were markedly enhanced by simultaneous inhibition of XPO1 in vitro. The combination of BMN673 and the XPO1 inhibitor selinexor inhibited primary SCLC cell proliferation in mini-patient-derived xenotransplants (miniPDXs) and markedly inhibited tumor growth without significant toxicity in xenograft models. The efficacy was enhanced for more than 2.5 times, compared to the single agent. Based on these findings, we further designed a novel dual PARP-XPO1 inhibitor and showed its effectiveness in SCLC. In this work, we illustrated that combining a PARP inhibitor with an XPO1 inhibitor is associated with significantly improved efficacy and tolerability. Dual PARP-XPO1 inhibition restored the FOXO3a balance and activity in SCLC. Collectively, targeting PARP1 and XPO1 opens new avenues for therapeutic intervention against SCLC, warranting further investigation in potential clinical trials.


Asunto(s)
Proteína Forkhead Box O3/metabolismo , Hidrazinas/administración & dosificación , Carioferinas/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Ftalazinas/administración & dosificación , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Triazoles/administración & dosificación , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citoplasma/metabolismo , Sinergismo Farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Hidrazinas/farmacología , Neoplasias Pulmonares/metabolismo , Ratones , Ftalazinas/farmacología , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Triazoles/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína Exportina 1
18.
J Phys Chem Lett ; 11(6): 2150-2157, 2020 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-32090570

RESUMEN

Matchstick-like Ag2S-ZnS nanorods (NRs) with a tunable aspect ratio (AR) were synthesized using one-pot thermal decomposition. The ultraviolet photoelectron spectra and time-resolved photoluminescence spectra of the Ag2S-ZnS NRs were collected to study their electronic band structures and charge carrier dynamics. The energy difference (ΔE) at the interface between the ZnS stem and Ag2S tip was altered as the AR of Ag2S-ZnS NRs increased from 11.9 to 18.4, resulting in an enlarged driving force for the delocalized electrons along the conduction band of ZnS being injected into that of Ag2S. The interfacial electron transfer rate constant (ket) from ZnS to Ag2S could be enhanced by ∼2 orders of magnitude from 5.27 × 106 to 3.24 × 108 s-1, leading to a significant improvement in the efficiency of solar hydrogen generation. This investigation provides new physical insights into the manipulation of charge carrier dynamics by means of AR adjustment in semiconductor nanoheterostructures for photoelectric conversions.

19.
ACS Nano ; 13(4): 4290-4301, 2019 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-30883107

RESUMEN

A deficiency of nitric oxide (NO) supply has been found to impair wound healing. The exogenous topical delivery of NO is a promising approach to enhance vasodilation and stimulate angiogenesis and collagen deposition. In this study, the CN groups on the surface of Prussian blue (PB) nanocubes were carefully reduced to -CH2-NH2 to conjugate with COOH group of hemin consisting of a Fe-porphyrin structure with strong affinity toward NO. Accordingly, the NO gas was able to coordinate to hemin-modified PB nanocubes. The hemin-modified PB carrying NO (PB-NO) can be responsible to near-infrared (NIR) light (808 nm) exposure to induce the thermo-induced liberation of NO based on the light-to-heat transformation property of PB nanocubes. The NO supply on the incisional wound sites can be readily topically dropped the colloidal solution of PB-NO for receiving NIR light irradiation. The enhanced blood flow was in a controllable manner whenever the wound sites containing PB-NO received NIR light irradiation. The promotion of blood perfusion following the on-demand multidelivery of NO has effectively facilitated the process of wound closure to enhance angiogensis and collagen deposition.


Asunto(s)
Coloides/química , Hemina/química , Nanopartículas/química , Neovascularización Fisiológica/efectos de los fármacos , Donantes de Óxido Nítrico/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular , Colágeno/metabolismo , Preparaciones de Acción Retardada/química , Femenino , Ferrocianuros/química , Humanos , Luz , Ratones Endogámicos C57BL , Microcirculación/efectos de los fármacos , Óxido Nítrico/administración & dosificación , Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/farmacología
20.
Adv Mater ; 31(49): e1905087, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31625638

RESUMEN

Chromium-doped zinc gallate, ZnGa2 O4 :Cr3+ (ZGC), is viewed as a long-lasting luminescence (LLL) phosphor that can avoid tissue autofluorescence interference for in vivo imaging detection. ZGC is a cubic spinel structure, a typical agglomerative or clustered morphology lacking a defined cubic shape, but a sphere-like feature is commonly obtained for the nanometric ZGC. The substantial challenge remains achieving a well-defined cubic feature in nanoscale. The process by which dispersed and well-defined concave cubic ZGC is obtained is described, exhibiting much stronger LLL in UV and X-ray excitation for the dispersed cubic ZGC compared with the agglomerative form that cannot be excited using X-rays with a low dose of 0.5 Gy. The cubic ZGC reveals a specific accumulation in liver and 0.5 Gy used at the end of X-ray excitation is sufficient for imaging of deep-seated hepatic tumors. The ZGC nanocubes show highly passive targeting of orthotopic hepatic tumors.


Asunto(s)
Cromo/análisis , Neoplasias Hepáticas/diagnóstico por imagen , Sustancias Luminiscentes/análisis , Nanopartículas/análisis , Zinc/análisis , Animales , Células Hep G2 , Humanos , Luminiscencia , Mediciones Luminiscentes/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Imagen Óptica/métodos , Rayos X
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