Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros

Métodos Terapêuticos e Terapias MTCI
Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Nanobiotechnology ; 21(1): 132, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081432

RESUMO

Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000-1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Fototerapia/métodos , Linhagem Celular Tumoral , Terapia Fototérmica , Polímeros , Morte Celular Imunogênica , Neoplasias/tratamento farmacológico , Técnicas Fotoacústicas/métodos
2.
J Nanobiotechnology ; 20(1): 193, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440088

RESUMO

BACKGROUND: Different from Fe ions in Fenton reaction, Mn ions can function both as catalyst for chemodynamic therapy and immune adjuvant for antitumor immune responses. In Mn-mediated Fenton-like reaction, bicarbonate ([Formula: see text]), as the most important component to amplify therapeutic effects, must be present, however, intracellular [Formula: see text] is strictly limited because of the tight control by live cells. RESULTS: Herein, Stimuli-responsive manganese carbonate-indocyanine green complexes (MnCO3-ICG) were designed for intracellular marriage of bicarbonate and Mn ions as "immune ion reactors" to regulate intracellular redox homeostasis and antitumor immune responses. Under the tumor acidic environment, the biodegradable complex can release "ion reactors" of Mn2+ and [Formula: see text], and ICG in the cytoplasm. The suddenly increased [Formula: see text] in situ inside the cells regulate intracellular pH, and accelerate the generation of hydroxyl radicals for the oxidative stress damage of tumors cells because [Formula: see text] play a critical role to catalyze Mn-mediated Fenton-like reaction. Investigations in vitro and in vivo prove that the both CDT and phototherapy combined with Mn2+-enhanced immunotherapy effectively suppress tumor growth and realize complete tumor elimination. CONCLUSIONS: The combination therapy strategy with the help of novel immune adjuvants would produce an enhanced immune response, and be used for the treatment of deep tumors in situ.


Assuntos
Bicarbonatos , Neoplasias , Bicarbonatos/uso terapêutico , Linhagem Celular Tumoral , Homeostase , Humanos , Imunidade , Neoplasias/tratamento farmacológico , Oxirredução
3.
J Nanobiotechnology ; 19(1): 419, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903233

RESUMO

Accurate diagnosis and effective treatment of primary liver tumors are of great significance, and optical imaging has been widely employed in clinical imaging-guided surgery for liver tumors. The second near-infrared window (NIR-II) emissive AIEgen photosensitizers have attracted a lot of attention with higher-resolution bioimaging and deeper penetration. NIR-II aggregation-induced emission-based luminogen (AIEgen) photosensitizers have better phototherapeutic effects and accuracy of the image-guided surgery/phototherapy. Herein, an NIR-II AIEgen phototheranostic dot was proposed for NIR-II imaging-guided resection surgery and phototherapy for orthotopic hepatic tumors. Compared with indocyanine green (ICG), the AIEgen dots showed bright and sharp NIR-II emission at 1250 nm, which extended to 1600 nm with high photostability. Moreover, the AIEgen dots efficiently generated reactive oxygen species (ROS) for photodynamic therapy. Investigations of orthotopic liver tumors in vitro and in vivo demonstrated that AIEgen dots could be employed both for imaging-guided tumor surgery of early-stage tumors and for 'downstaging' intention to reduce the size. Moreover, the therapeutic strategy induced complete inhibition of orthotopic tumors without recurrence and with few side effects.


Assuntos
Antineoplásicos , Neoplasias Hepáticas , Fármacos Fotossensibilizantes , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cirurgia Assistida por Computador/métodos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia
4.
SLAS Discov ; 26(8): 1040-1054, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34130529

RESUMO

One of the main reasons for the lack of drug efficacy in late-stage clinical trials is the lack of specific and selective target engagement. To increase the likelihood of success of new therapeutics, one approach is to conduct proximal target engagement testing during the early phases of preclinical drug discovery. To identify and optimize selective IRAK4 inhibitors, a kinase that has been implicated in multiple inflammatory and autoimmune diseases, we established an electrochemiluminescence (ECL)-based cellular endogenous IRAK1 activation assay as the most proximal functional evaluation of IRAK4 engagement to support structure-activity relationship (SAR) studies. Since IRAK1 activation is dependent on both the IRAK4 scaffolding function in Myddosome formation and IRAK4 kinase activity for signal transduction, this assay potentially captures inhibitors with different mechanisms of action. Data from this IRAK1 assay with compounds representing different structural classes showed statistically significant correlations when compared with results from both IRAK4 biochemical kinase activity and functional peripheral blood mononuclear cell (PBMC)-derived tumor necrosis factor α (TNFα) secretion assays, validating the biological relevancy of the IRAK1 target engagement as a biomarker of the IRAK4 activity. Plate uniformity and potency reproducibility evaluations demonstrated that this assay is amenable to high throughput. Using Bland-Altman assay agreement analysis, we demonstrated that incorporating such proximal pharmacological assessment of cellular target engagement to an in vitro screening funnel for SAR studies can prevent compound optimization toward off-target activity.


Assuntos
Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Medições Luminescentes/métodos , Inibidores de Proteínas Quinases/farmacologia , Biomarcadores , Ativação Enzimática/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo
5.
Adv Mater ; 32(23): e2000377, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363649

RESUMO

Combination therapy based on nanomedicine has gained momentum in oncology in recent years, offering superior safety and efficacy over monotherapies. It is critical to design theranostics that are composed of imaging and therapeutic agents already approved. Herein, gadolinium (Gd)-rose bengal coordination polymer nanodots (GRDs) are reported. The GRDs exhibit a unique absorption property and 7.7-fold luminescence enhancement, as well as a 1.9-fold increase in singlet oxygen generation efficiency over free rose bengal. Meanwhile, GRDs exhibit a twofold increase in r1 relaxivity over gadopentetic acid (Gd-DTPA) and have better X-ray absorption ability than rose bengal alone. These excellent properties of the GRDs are verified both in vitro and in vivo. The combination of photodynamic therapy (PDT) and radiation therapy (RT) more significantly inhibits tumor growth than monotherapies (i.e., PDT or RT). This work offers a new route to designing and synthesizing Gd-based nanotheranostics for image-guided cancer therapy.


Assuntos
Complexos de Coordenação/química , Gadolínio/química , Fotoquimioterapia/métodos , Polímeros/química , Polímeros/uso terapêutico , Radioterapia Guiada por Imagem/métodos , Rosa Bengala/química , Animais , Linhagem Celular Tumoral , Imageamento por Ressonância Magnética , Camundongos , Nanomedicina , Nanopartículas/química , Imagem Óptica
6.
Bioconjug Chem ; 31(1): 82-92, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31809019

RESUMO

Manganese dioxide (MnO2) nanoparticles are a promising type of radiosensitizer for they can catalyze H2O2 decomposition to produce O2. Combining MnO2 nanoparticles with conventional, small molecule radiosensitizers would further enhance radiotherapy (RT) efficacy due to complementary mechanisms of action. However, solid MnO2 nanoparticles are suboptimal at drug loading, limiting the related progress. Herein we report a facile method to synthesize mesoporous MnO2 (mMnO2) nanoparticles, which can efficiently encapsulate small molecule therapeutics. In particular, we found that acridine orange (AO), a small molecule radiosensitizer, can be loaded onto mMnO2 nanoparticles at very high efficiency and released to the surroundings in a controlled fashion. We show that mMnO2 nanoparticles can efficiently produce O2 inside cells. This, together with AO-induced DNA damage, significantly enhances RT outcomes, which was validated both in vitro and in vivo. Meanwhile, mMnO2 nanoparticles slowly degrade in acidic environments to release Mn2+, providing a facile way to keep track of the nanoparticles through magnetic resonance imaging (MRI). Overall, our studies suggest mMnO2 as a promising nanoplatform that can be exploited to produce composite radiosensitizers for RT.


Assuntos
Laranja de Acridina/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Compostos de Manganês/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/radioterapia , Óxidos/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos Nus , Nanopartículas/ultraestrutura , Neoplasias/patologia
7.
Nanoscale ; 11(35): 16351-16361, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432837

RESUMO

Carbon-based light-activated materials can absorb optical energy to generate photoacoustic (PA) signals for imaging or transduce optical photons to thermal energy, which holds great promise for biomedical applications. Herein, we synthesize hollow and mesoporous carbon nanospheres (HMCNs) with uniform size on a large scale. The properties of hollow cavity and mesoporous structures make the HMCNs achieve high drug loading (480 mg DOX per g HMCNs). The present intense near infrared (NIR) absorbance achieves excellent photoacoustic imaging ability and photothermal conversion efficacy (32.0%). More interestingly, the encapsulated drugs can have a triggered release under NIR irradiation. The investigations in vitro and in vivo demonstrate that HMCNs have excellent biocompatibility, and accumulate in tumors by the enhanced permeability and retention (EPR) effect. Moreover, under NIR irradiation, in vivo evaluation shows that HMCNs can perform strong PA imaging, and induce great tumor inhibition by the combination of chemotherapy and PTT under the guidance of photoacoustic imaging. The present study provides new insight for design of novel biocompatible light-activated carbons for cancer nanotheranostics.


Assuntos
Carbono , Doxiciclina , Hipertermia Induzida , Nanosferas , Neoplasias Experimentais , Técnicas Fotoacústicas , Animais , Carbono/química , Carbono/farmacologia , Linhagem Celular Tumoral , Doxiciclina/química , Doxiciclina/farmacocinética , Doxiciclina/farmacologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanosferas/química , Nanosferas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Adv Mater ; 31(16): e1808024, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30848541

RESUMO

X-ray-induced photodynamic therapy (X-PDT) combines both the advantages of radiotherapy (RT) and PDT, and has considerable potential applications in clinical deep-penetrating cancer therapy. However, it is still a major challenge to prepare monodisperse nanoscintillators with uniform size and high light yield. In this study, a general and rapid synthesis method is presented that can achieve large-scale preparation of monodisperse and uniform silicate nanoscintillators. By simply adjusting the metal dopants, silicate nanoscintillators with controllable size and X-ray-excited optical luminescence (450-900 nm) are synthesized by employing a general ion-incorporated silica-templating method. To make full use of external radiation, the silicate nanoscintillators are conjugated with photosensitizer rose bengal and arginylglycylaspartic acid (RGD) peptide, making them intrinsically dual-modal targeted imaging probes. Both in vitro and in vivo experiments demonstrate that the silicate nanosensitizers can accumulate effectively in tumors and achieve significant inhibitory effect on tumor progression under low-dose X-ray irradiation, while minimally affecting normal tissues. The insights gained in this study may provide an attractive route to synthesize nanosensitizers to overcome some of the limitations of RT and PDT in cancer treatment.


Assuntos
Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Silicatos/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/química , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/química , Imagem Óptica , Permeabilidade , Fármacos Fotossensibilizantes/administração & dosagem , Rosa Bengala/química , Raios X
9.
ACS Appl Mater Interfaces ; 7(41): 23278-90, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26430876

RESUMO

To enhance the efficacy and optimize the treatment of cancers, the integration of multimodal treatment strategies leading to synergistic effects is a promising approach. The coassembly of multifunctional agents for systematic therapies has received considerable interest in cancer treatment. Herein, Ru(II) complex-functionalized single-walled carbon nanotubes (Ru@SWCNTs) are developed as nanotemplates for bimodal photothermal and two-photon photodynamic therapy (PTT-TPPDT). SWCNTs have the ability to load a great amount of Ru(II) complexes (Ru1 or Ru2) via noncovalent π-π interactions. The loaded Ru(II) complexes are efficiently released by the photothermal effect of irradiation from an 808 nm diode laser (0.25 W/cm(2)). The released Ru(II) complexes produce singlet oxygen species ((1)O2) upon two-photon laser irradiation (808 nm, 0.25 W/cm(2)) and can be used as a two-photon photodynamic therapy (TPPDT) agent. Based on the combination of photothermal therapy and two-photon photodynamic therapy, Ru@SWCNTs have greater anticancer efficacies than either PDT using Ru(II) complexes or PTT using SWCNTs in two-dimensional (2D) cancer cell and three-dimensional (3D) multicellular tumor spheroid (MCTS) models. Furthermore, in vivo tumor ablation is achieved with excellent treatment efficacy under a diode laser (808 nm) irradiation at the power density of 0.25 W/cm(2) for 5 min. This study examines an efficacious bimodal PTT and TPPDT nanoplat form for the development of cancer therapeutics.


Assuntos
Hipertermia Induzida , Raios Infravermelhos , Nanotubos de Carbono/química , Fotoquimioterapia , Rutênio/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Endocitose/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Camundongos Nus , Nanotubos de Carbono/ultraestrutura , Fótons , Oxigênio Singlete/química , Espectrofotometria Ultravioleta , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA