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1.
Cell ; 186(26): 5719-5738.e28, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38056463

RESUMO

Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brain metastases. Although other factors beyond mechanical obstructions have been suggested, the exact mechanisms are unknown. Using single-nucleus RNA sequencing and spatial transcriptomics, we find that a distinct population of mast cells locate in the choroid plexus and dramatically increase during TAH. Genetic fate tracing and intracranial mast-cell-specific tryptase knockout showed that choroid plexus mast cells (CPMCs) disrupt cilia of choroid plexus epithelia via the tryptase-PAR2-FoxJ1 pathway and consequently increase cerebrospinal fluid production. Mast cells are also found in the human choroid plexus. Levels of tryptase in cerebrospinal fluid are closely associated with clinical severity of TAH. BMS-262084, an inhibitor of tryptase, can cross the blood-brain barrier, inhibit TAH in vivo, and alleviate mast-cell-induced damage of epithelial cilia in a human pluripotent stem-cell-derived choroid plexus organoid model. Collectively, we uncover the function of CPMCs and provide an attractive therapy for TAH.


Assuntos
Neoplasias Encefálicas , Plexo Corióideo , Hidrocefalia , Mastócitos , Humanos , Neoplasias Encefálicas/secundário , Plexo Corióideo/metabolismo , Plexo Corióideo/patologia , Hidrocefalia/metabolismo , Hidrocefalia/patologia , Mastócitos/metabolismo , Mastócitos/patologia , Triptases/líquido cefalorraquidiano , Metástase Neoplásica/patologia
2.
J Am Chem Soc ; 142(5): 2490-2496, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31944687

RESUMO

The limited efficacy of single-agent immune checkpoint inhibitors in treating tumors has prompted investigations on their combination partners. Here, a tumor-homing indoleamine 2,3-dioxygenase (IDO) nanoinhibitor is reported to selectively inhibit immunosuppressive IDO pathway in the tumor microenvironment. It is self-assembled from a modularly designed peptide-drug conjugate containing a hydrophilic targeting motif (arginyl-glycyl-aspartic acid; RGD), two protonatable histidines, and an ester bond-linked hydrophobic IDO inhibitor, which exhibits pH-responsive disassembly and esterase-catalyzed drug release. Markedly, it achieved potent and persistent inhibition of intratumoral IDO activity with a reduced systemic toxicity, which greatly enhanced the therapeutic efficacy of programmed cell death-ligand 1 blockade in vivo. Overall, this study provides a promising paradigm of combinatorial normalization immunotherapy by exploiting a targeted IDO nanoinhibitor to augment the antitumor immunity of checkpoint inhibitors.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Desenho de Fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Nanopartículas , Pró-Fármacos/farmacologia , Humanos , Imunoterapia , Oligopeptídeos/química , Pró-Fármacos/farmacocinética , Microambiente Tumoral
3.
Environ Sci Technol ; 53(15): 9128-9138, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31268311

RESUMO

The Spring Festival is the most important holiday in China. During this time, the levels of particulate matter (PM) as well as gaseous copollutants significantly increase because of the widespread enjoyment of fireworks. The expression patterns of microRNAs may serve as valuable signatures of exposure to environmental constituents. We exposed macrophages to the whole stream of outdoor air at the air-liquid interface aiming at closely approximating the physiological conditions and the inhalation situation in the lung. 58 miRNAs were up-regulated, and 68 miRNAs were down-regulated in the night of the New Year's Eve (exposure group E2N1) compared to filtered-air exposed control cells. The target genes of the up-regulated miRNAs were enriched in immunity- and inflammation-linked pathways, such as the TLR-NF-κB pathway. Compared to the E2N1 group, 29 miRNAs were up-regulated, and 23 miRNAs were down-regulated in the cells exposed to air from the daytime of the Chinese New Year with higher concentrations of particles, SO2, and nitrogen oxide. The target genes of the up-regulated miRNAs were mostly enriched in apoptosis, adhesion, and junction-related pathways. These results preliminarily unravel part of the toxic mechanisms of air constituents and provide clues for discovering the main drivers of air pollution-induced disorders.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , China , Monitoramento Ambiental , Férias e Feriados , Material Particulado
4.
Angew Chem Int Ed Engl ; 57(9): 2377-2382, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29359840

RESUMO

Cysteine-based chiral optically active carbon dots (CDs) and their effects on cellular energy metabolism, which is vital for essential cellular functions, have been barely reported. A green and effective synthesis strategy for chiral N-S-doped CDs (fluorescence quantum yield ca. 41.26 %) based on hydrothermal treatment of l- or d-cysteine at as low as 60 °C has been developed. This suggested that cysteine was instable in aqueous solutions and acts as a warning for high-temperature synthesis of nanomaterials using cysteine as stabilizer. Human bladder cancer T24 cells treated with l-CDs showed up-regulated glycolysis, while d-CDs had no similar effects. In contrast, no disturbance to the basal mitochondrial aerobic respiration of T24 cells was caused by either chiral CD.


Assuntos
Carbono/metabolismo , Cisteína/metabolismo , Metabolismo Energético , Fluorescência , Pontos Quânticos/metabolismo , Carbono/química , Linhagem Celular Tumoral , Cisteína/química , Humanos , Concentração de Íons de Hidrogênio , Imagem Óptica , Pontos Quânticos/química
5.
Nanomedicine ; 12(2): 439-48, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26711964

RESUMO

Nanomaterial-mediated photothermal therapy has shown great potential to fulfill the unmet medical needs for treatment of tumors. In this study, a rod-like gold nanoshell capsule, which can offer both photothermal therapy and chemotherapy, is synthesized and applied for the treatment of melanoma. This nano-platform is made by developing a gold nanoshell on rod-like mesoporous silica nanoparticles with different aspect ratios, and it was found that the aspect ratio significantly influenced the cellular uptake and tumor distribution of the nanoparticles. The gold nanoshell capsules with a moderate aspect ratio are found to be efficiently taken up by melanoma cells and are able to penetrate tumor tissues, resulting in the effective ablation of highly malignant melanomas when used along with mild laser irradiation and a single treatment. This study demonstrates that the optimization of the aspect ratio is indispensable to further development of this nanoplatform for antitumor therapy. FROM THE CLINICAL EDITOR: The combination of hyperthermia and chemotherapeutic agents has been investigated as a new approach for the treatment of malignant melanoma. It appears that the aspect ratio may play an important role in the treatment efficacy. In this article, the authors studied how the AR influenced the cellular uptake and the optimal AR for antitumor effects.


Assuntos
Antineoplásicos/uso terapêutico , Ouro/uso terapêutico , Melanoma Experimental/terapia , Nanoconchas/uso terapêutico , Taxoides/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Terapia Combinada , Docetaxel , Feminino , Ouro/química , Hipertermia Induzida , Melanoma Experimental/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoconchas/química , Nanoconchas/ultraestrutura , Fototerapia , Taxoides/administração & dosagem
6.
Front Pharmacol ; 15: 1338725, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495096

RESUMO

Introduction: The toxicity of arsenic is widely recognized globally, mainly harming human health by polluting water, soil, and food. However, its formulations can also be used for the clinical treatment of diseases such as leukemia and tumors. Arsenic has been used as a drug in China for over 2,400 years, with examples such as the arsenic-containing drug realgar mentioned in Shennong's Herbal Classic. We have reviewed references on arsenic over the past thirty years and found that research has mainly focused on clinical, pharmacological, and toxicological aspects. Results and Discussion: The finding showed that in clinical practice, arsenic trioxide is mainly used in combination with all-trans retinoic acid (ATRA) at a dose of 10 mg/d for the treatment of acute promyelocytic leukemia (APL); realgar can be used to treat acute promyelocytic leukemia, myelodysplastic syndrome, and lymphoma. In terms of pharmacology, arsenic mainly exerts anti-tumor effects. The dosage range of the action is 0.01-80 µmol/L, and the concentration of arsenic in most studies does not exceed 20 µmol/L. The pharmacological effects of realgar include antiviral activity, inhibition of overactivated lactate dehydrogenase, and resistance to malaria parasites. In terms of toxicity, arsenic is toxic to multiple systems in a dose-dependent manner. For example, 5 µmol/L sodium arsenite can induce liver oxidative damage and promote the expression of pro-inflammatory factors, and 15 µmol/L sodium arsenite induces myocardial injury; when the concentration is higher, it is more likely to cause toxic damage.

7.
Cancer Lett ; 560: 216138, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36934836

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with insidious onset and early distal metastasis. Metabolic reprogramming, the autonomous changes in cellular bioenergetics driven by aberrant genetic events and crosstalk between cancer and non-cancer cells in the desmoplastic microenvironment, is pivotal for the rapid progression of PDAC. As an attractive therapeutic target, nucleoside metabolism is regulated by various anti-metabolic drugs for the clinical treatment of PDAC. Despite various challenges, such as poor drug delivery efficiency and off-target side effects, metabolic modification and intervention are emerging as promising strategies for PDAC therapy, enabled by the rapid development of nanotechnology-based drug delivery strategies. In this review, we discuss the metabolic characteristics of PDAC and highlight how the development of nanomedicine has boosted the development of new therapeutics for PDAC by modulating critical targets in metabolic reprogramming.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Metabolismo Energético , Nanomedicina , Microambiente Tumoral , Neoplasias Pancreáticas
8.
Front Pharmacol ; 14: 1230608, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38235111

RESUMO

This review discusses the variety, chemical composition, pharmacological effects, toxicology, and clinical research of corals used in traditional medicine in the past two decades. At present, several types of medicinal coral resources are identified, which are used in 56 formulas such as traditional Chinese medicine, Tibetan medicine, Mongolian medicine, and Uyghur medicine. A total of 34 families and 99 genera of corals are involved in medical research, with the Alcyoniidae family and Sarcophyton genus being the main research objects. Based on the structural types of compounds and the families and genera of corals, this review summarizes the compounds primarily reported during the period, including terpenoids, steroids, nitrogen-containing compounds, and other terpenoids dominated by sesquiterpene and diterpenes. The biological activities of coral include cytotoxicity (antitumor and anticancer), anti-inflammatory, analgesic, antibacterial, antiviral, immunosuppressive, antioxidant, and neurological properties, and a detailed summary of the mechanisms underlying these activities or related targets is provided. Coral toxicity mostly occurs in the marine ornamental soft coral Zoanthidae family, with palytoxin as the main toxic compound. In addition, nonpeptide neurotoxins are extracted from aquatic corals. The compatibility of coral-related preparations did not show significant acute toxicity, but if used for a long time, it will still cause toxicity to the liver, kidneys, lungs, and other internal organs in a dose-dependent manner. In clinical applications, individual application of coral is often used as a substitute for orthopedic materials to treat diseases such as bone defects and bone hyperplasia. Second, coral is primarily available in the form of compound preparations, such as Ershiwuwei Shanhu pills and Shanhu Qishiwei pills, which are widely used in the treatment of neurological diseases such as migraine, primary headache, epilepsy, cerebral infarction, hypertension, and other cardiovascular and cerebrovascular diseases. It is undeniable that the effectiveness of coral research has exacerbated the endangered status of corals. Therefore, there should be no distinction between the advantages and disadvantages of listed endangered species, and it is imperative to completely prohibit their use and provide equal protection to help them recover to their normal numbers. This article can provide some reference for research on coral chemical composition, biological activity, chemical ecology, and the discovery of marine drug lead compounds. At the same time, it calls for people to protect endangered corals from the perspectives of prohibition, substitution, and synthesis.

9.
Nat Commun ; 14(1): 5178, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620331

RESUMO

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.


Assuntos
Hipertermia Induzida , Nanopartículas Metálicas , Neoplasias , Feminino , Animais , Camundongos , Ouro , Nanopartículas Metálicas/uso terapêutico , Hipertermia , Receptores Toll-Like , Neoplasias/terapia , Citocinas , Imunidade
10.
Small ; 8(3): 404-12, 2012 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-22144073

RESUMO

Evaluation of systemic biosafety of nanomaterials urgently demands a comprehensive understanding of the mechanisms of the undesirable interference and systemic signaling that arises between man-made nanomaterials and biological systems. It is shown that exosomes may act as signal conveyors for nanoparticle-induced systemic immune responses. Exosomes are extracellularly secreted membrane vesicles which act as Trojan horses for the dissemination and intercellular communication of natural nanosized particles (like viruses). Upon exposure to magnetic iron oxide nanoparticles (MIONs), it is possible to dose-dependently generate a significant number of exosomes in the alveolar region of BALB/c mice. These exosomes are quickly eliminated from alveoli into systemic circulation and largely transfer their signals to the immune system. Maturation of dendritic cells and activation of splenic T cells are significantly induced by these exosomes. Furthermore, exosome-induced T-cell activation is more efficient toward sensitized T cells and in ovalbumin (OVA)-sensitized mice than in the unsensitized counterparts. Activation of systemic T cells reveals a T helper 1 polarization and aggravated inflammation, which poses potential hazards to the deterioration of allergic diseases in OVA-sensitized mice. The studies suggest that exosomes may act as conveyors for extrapulmonary signal transduction in nanoparticle-induced immune systemic responses, which are the key in vivo processes of manufactured nanoparticles executing either biomedical functions or toxic responses.


Assuntos
Exossomos/imunologia , Imunidade/imunologia , Pulmão/imunologia , Nanopartículas de Magnetita/química , Transdução de Sinais/imunologia , Animais , Líquido da Lavagem Broncoalveolar , Diferenciação Celular/imunologia , Polaridade Celular/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Exossomos/ultraestrutura , Imunização , Inflamação/imunologia , Inflamação/patologia , Pulmão/patologia , Ativação Linfocitária/imunologia , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Modelos Imunológicos , Ovalbumina/imunologia , Células Th1/citologia , Células Th1/imunologia
11.
Small ; 8(18): 2841-8, 2012 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-22674628

RESUMO

The mechanisms associated with the induction of systemic immune responses by nanoparticles are not fully understood, but their elucidation is critical to address safety issues associated with the broader medical application of nanotechnology. In this study, a key role of nanoparticle-induced exosomes (extracellularly secreted membrane vesicles) as signaling mediators in the induction of T helper cell type 1 (Th1) immune activation is demonstrated. In vivo exposure to magnetic iron oxide nanoparticles (MIONs) results in significant exosome generation in the alveolar region of Balb/c mice. These act as a source of nanoparticle-induced, membrane-bound antigen/signaling cargo, which transfer their components to antigen-presenting cells (APCs) in the reticuloendothelial system. Through exosome-initiated signals, immature dendritic cells (iDCs) undergo maturation and differentiation to the DC1 subtype, while macrophages go through classical activation and differentiation to the M1 subtype. Simultaneously, iDCs and macrophages release various Th1 cytokines (including interleukin-12 and tumor necrosis factor α) driving T-cell activation and differentiation. Activated APCs (especially DC1 and M1 subtypes) consequently prime T-cell differentiation towards a Th1 subtype, thereby resulting in an orchestrated Th1-type immune response. Th1-polarized immune activation is associated with delayed-type hypersensitivity, which might underlie the long-term inflammatory effects frequently associated with nanoparticle exposure. These studies suggest that nanoparticle-induced exosomes provoke the immune activation and inflammatory responses that can accompany nanoparticle exposure.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Exossomos/metabolismo , Compostos Férricos/imunologia , Nanopartículas de Magnetita/administração & dosagem , Células Th1/imunologia , Animais , Diferenciação Celular , Citocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Compostos Férricos/química , Ativação Linfocitária , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Nanopartículas de Magnetita/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Th1/citologia
12.
Nat Rev Mater ; 6(9): 766-783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026278

RESUMO

Biomolecule-based nanostructures are inherently multifunctional and harbour diverse biological activities, which can be explored for cancer nanomedicine. The supramolecular properties of biomolecules can be precisely programmed for the design of smart drug delivery vehicles, enabling efficient transport in vivo, targeted drug delivery and combinatorial therapy within a single design. In this Review, we discuss biomolecule-based nanostructures, including polysaccharides, nucleic acids, peptides and proteins, and highlight their enormous design space for multifunctional nanomedicines. We identify key challenges in cancer nanomedicine that can be addressed by biomolecule-based nanostructures and survey the distinct biological activities, programmability and in vivo behaviour of biomolecule-based nanostructures. Finally, we discuss challenges in the rational design, characterization and fabrication of biomolecule-based nanostructures, and identify obstacles that need to be overcome to enable clinical translation.

13.
ACS Nano ; 15(9): 14149-14161, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34478262

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) cells are surrounded by a dense extracellular matrix (ECM), which greatly restricts the access of therapeutic agents, resulting in poor clinical response to chemotherapy. Transforming growth factor-ß1 (TGF-ß1) signaling plays a crucial role in construction of the desmoplastic stroma and provides potential targets for PDAC therapy. To surmount the pathological obstacle, we developed a size switchable nanosystem based on PEG-PLGA nanospheres encapsulated within liposomes for the combined delivery of vactosertib (VAC), a TGF-ß1 receptor kinase inhibitor, and the cytotoxic drug paclitaxel (TAX). By surface modification of the liposomes with a peptide, APTEDB, the nanosystem can be anchored to abundant tumor-associated fibronectin in PDAC stroma and decreases its size by releasing encapsulated TAX-loaded nanospheres, as well as VAC after collapse of the liposomes. The inhibition of ECM hyperplasia by VAC allows TAX more ready access to the cancer cells in addition to its small size, thereby shrinking pancreatic tumor xenografts more effectively than a combination of the free drugs. This size switchable nanosystem enables sequential delivery of drugs at a fixed dose combination with simplified administration and provides an encouraging cascade approach of drug penetration for enhanced chemotherapy in cancers with a dense desmoplastic stroma.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma , Carcinoma Ductal Pancreático/tratamento farmacológico , Transformação Celular Neoplásica , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Fator de Crescimento Transformador beta/antagonistas & inibidores
14.
Sci Transl Med ; 13(601)2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233949

RESUMO

Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on Escherichia coli cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8+ T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer.


Assuntos
Vacinas Anticâncer , Melanoma Experimental , Adjuvantes Imunológicos , Animais , Linfócitos T CD8-Positivos , Membrana Celular , Células Dendríticas , Humanos , Camundongos , Camundongos Endogâmicos C57BL
15.
Biomaterials ; 232: 119745, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31918228

RESUMO

Solid tumors, especially desmoplastic tumors, are characterized by a dense fibrotic stroma composed of abundant cancer-associated fibroblasts and excessive extracellular matrix. These physical barriers seriously compromise drug delivery to tumor cells, leading to suboptimal treatment efficacy and resistance to current tumor-centric therapeutics. The need to overcome these problems has driven extensive investigations and sparked the flourish of anti-stromal therapy, particularly in the field of nanomedicines. In this paper, we firstly review the major components of the tumor stroma and discuss their impact on drug delivery. Then, according to the different stromal targets, we summarize the current status of anti-stromal therapy and highlight recent advances in anti-stromal nanomedicines. We further examine the potential of nano-enabled anti-stromal therapy to enhance the anti-tumor efficacy of other therapeutic modalities, including chemotherapy, immunotherapy, phototherapy and radiotherapy. Finally, the potential concerns and future developments of anti-stromal nanomedicines are discussed.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia , Nanomedicina , Neoplasias/tratamento farmacológico
16.
Adv Mater ; 32(31): e2000038, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32596808

RESUMO

Fenton reaction-mediated oncotherapy is an emerging strategy which uses iron ions to catalytically convert endogenous hydrogen peroxide into hydroxyl radicals, the most reactive oxygen species found in biology, for efficient cancer therapy. However, Fenton reaction efficiency in tumor tissue is typically limited due to restrictive conditions. One strategy to overcome this obstacle is to increase the temperature specifically at the tumor site. Herein, a tumor-targeting iron sponge (TTIS) nanocomposite based on graphdiyne oxide, which has a high affinity for iron is described. TTIS can accumulate in tumor tissue by decoration with a tumor-targeting polymer to enable tumor photoacoustic and magnetic resonance imaging. With its excellent photothermal conversion efficiency (37.5%), TTIS is an efficient photothermal therapy (PTT) agent. Moreover, the heat produced in the process of PTT can accelerate the release of iron ions from TTIS and simultaneously enhance the efficiency of the Fenton reaction, thus achieving a combined PTT and Fenton reaction-mediated cancer therapy. This work introduces a graphdiyne oxide-based iron sponge that exerts an enhanced antitumor effect through PTT and Fenton chemistry.


Assuntos
Grafite/química , Peróxido de Hidrogênio/química , Ferro/química , Nanocompostos/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Óxido Ferroso-Férrico/química , Hemólise/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Hipertermia Induzida , Camundongos , Camundongos Endogâmicos BALB C , Nanocompostos/toxicidade , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Neoplasias/terapia , Fototerapia , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Ensaios Antitumorais Modelo de Xenoenxerto
17.
ACS Appl Mater Interfaces ; 11(49): 45416-45426, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31713410

RESUMO

Local surface plasmon resonance (LSPR)-enhanced catalysis has attracted much attention recently. Palladium nanoparticles have been reported to have various nanozyme activities and exhibit promising potentials for biomedical applications. However, as Pd is a poor plasmonic metal, little attention has been paid to its LSPR-regulated nanozyme activity. Herein, by using Au nanorods (AuNRs) as a strong plasmonic core, we coated a thin layer Pd to form a rod-shaped core-shell structure. The obtained Au@PdNRs showed tunable LSPR bands in the near-infrared (NIR) spectral range inheriting from the Au core and yet an exposed Pd surface for catalysis. The oxidase-like activity was investigated in the dark and upon SPR excitation. The plasmon-enhanced activity was observed and was mainly ascribed to the local photothermal effect. Finally, to enhance biocompatibility, mesoporous silica-coated nanorods were used to detect the oxidase-like activity in cells. After being endocytosed by cells, upon plasmon excitation, the oxidase activity of Au@PdNRs could be manifested and lead to higher cytotoxicity and depolarization of mitochondrial membrane potential. Our studies highlight the feasibility of regulating the nanozyme activity of plasmonic nanostructures using their unique NIR plasmonic features with spatiotemporal control.


Assuntos
Nanopartículas Metálicas/química , Nanotubos/química , Oxirredutases/química , Paládio/química , Catálise , Ouro/química , Nanoestruturas/química , Dióxido de Silício/química , Ressonância de Plasmônio de Superfície
18.
ACS Appl Mater Interfaces ; 11(36): 32798-32807, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31430113

RESUMO

Graphdiyne has attracted much interest from researchers for their potential applications in energy storage, catalysis, and biomedical areas. As one of the derivatives of graphdiyne, graphdiyne quantum dots (GDQDs) may possess superior bioactivity due to active acetylene units. However, the biological application of biocompatible GDQDs have not been reported so far. Herein, GDQDs with uniform size and good crystallization were prepared via a classical solvothermal method. The GDQDs exhibit excitation- and pH-dependent fluorescence emission as well as superior photostability, demonstrating their potential for bioimaging. The GDQDs demonstrate efficient cellular uptake and cell imaging without induction of detectable cytotoxic effects in vitro. Systematical safety evaluation further confirmed good biocompatibility of the GDQDs in vivo. Our study preliminarily validates the application of the GDQDs in biomedicine and encourages more thorough studies for better realizing the potential of GDQDs.


Assuntos
Materiais Biocompatíveis/química , Grafite/química , Imagem Molecular , Pontos Quânticos/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Linhagem Celular Tumoral , Eritrócitos/efeitos dos fármacos , Grafite/síntese química , Grafite/toxicidade , Hemólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Fenômenos Ópticos , Pontos Quânticos/toxicidade
19.
ACS Nano ; 13(4): 4379-4391, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30901191

RESUMO

Combining informative imaging methodologies with effective treatments to destroy tumors is of great importance for oncotherapy. Versatile nanotheranostic agents that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable to meet these requirements. Here, a simple but powerful nanoplatform based on polydopamine-coated gold nanostar (GNS@PDA), which can be easily diversified to achieve various function extensions, is designed to realize functional and anatomical imaging-guided photothermal oncotherapy. This nanoplatform intrinsically enables computed tomography/photoacoustic/two-photon luminescence/infrared thermal tetramodal imaging and can further incorporate fibroblast activation protein (FAP, a protease highly expressed in most of tumors) activatable near-infrared fluorescence imaging and Fe3+-based magnetic resonance imaging for comprehensive diagnosis. Moreover, GNS@PDA exhibits excellent photothermal performance and efficient tumor accumulation. Under the precise guidance of multimodal imaging, GNS@PDA conducts homogeneous photothermal ablation of bulky solid tumors (∼200 mm3) in a xenograft mouse model. These results suggest great promise of this extendable nanoplatform for cancer theranostics.


Assuntos
Ouro/uso terapêutico , Hipertermia Induzida , Indóis/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/terapia , Polímeros/uso terapêutico , Nanomedicina Teranóstica , Células 3T3 , Animais , Linhagem Celular Tumoral , Humanos , Hipertermia Induzida/métodos , Camundongos , Camundongos Nus , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos
20.
Adv Mater ; 31(15): e1808200, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30773718

RESUMO

Photodynamic therapy (PDT) is a promising anticancer treatment and is clinically approved for different types of tumors. However, current PDT suffers several obstacles, including its neutralization by excess glutathione (GSH) in the tumor tissue and its strongly proangiogenic tumor response. In this work, a biomimic, multifunctional nanoparticle-based PDT agent, combining a tumor-targeted photosensitizer with GSH scavenging and antiangiogenesis therapy, is developed. A porphyrinic Zr-metal-organic framework nanoparticle is used simultaneously as the photosensitizer and the delivery vehicle of vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib. The core nanoparticles are wrapped in MnO2 to consume the intratumoral GSH and then decorated with a tumor cell membrane camouflage. After intravenous administration, the nanoparticles selectively accumulate in tumor through homotypic targeting mediated by the biomimic decoration, and the combination of enhanced PDT and antiangiogenic drug significantly improves their tumor inhibition efficiency. This study provides an integrated solution for mechanism-based enhancement of PDT and demonstrates the encouraging potential for multifunctional nanosystem applicable for tumor therapy.


Assuntos
Inibidores da Angiogênese , Antineoplásicos/química , Materiais Biomiméticos , Nanopartículas Metálicas , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Humanos , Estruturas Metalorgânicas , Camundongos Endogâmicos BALB C , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
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