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1.
Am J Pathol ; 194(9): 1712-1723, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38897537

RESUMO

Lung cancer is an increasingly serious health problem worldwide, and early detection and diagnosis are crucial for successful treatment. With the development of artificial intelligence and the growth of data volume, machine learning techniques can play a significant role in improving the accuracy of early detection in lung cancer. This study proposes a deep learning-based segmentation algorithm for rapid on-site cytopathological evaluation (ROSE) to enhance the diagnostic efficiency of endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA) during surgery. By utilizing the CUNet3+ network model, cell clusters, including cancer cell clusters, can be accurately segmented in ROSE-stained pathological sections. The model demonstrated high accuracy, with an F1-score of 0.9604, recall of 0.9609, precision of 0.9654, and accuracy of 0.9834 on the internal testing data set. It also achieved an area under the receiver-operating characteristic curve of 0.9972 for cancer identification. The proposed algorithm saved time for on-site diagnosis, improved EBUS-TBNA efficiency, and outperformed classical segmentation algorithms in accurately identifying lung cancer cell clusters in ROSE-stained images. It effectively reduced over-segmentation, decreased network parameters, and enhanced computational efficiency, making it suitable for real-time patient evaluation during surgical procedures.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Algoritmos
2.
Opt Express ; 32(6): 9747-9766, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571201

RESUMO

We investigated secondary cavitation bubble dynamics during laser-induced bubble formation in a small container with a partially confined free surface and elastic thin walls. We employed high-speed photography to record the dynamics of sub-mm-sized laser-induced bubbles and small secondary bubble clouds. Simultaneous light scattering and acoustic measurements were used to detect the oscillation times of laser-induced bubbles. We observed that the appearance of secondary bubbles coincides with a prolonged collapse phase and with re-oscillations of the laser-induced bubble. We observed an asymmetric distribution of secondary bubbles with a preference for the upstream side of the focus, an absence of secondary bubbles in the immediate vicinity of the laser focus, and a migration of laser-induced bubble toward secondary bubbles at large pulse energies. We found that secondary bubbles are created through heating of impurities to form initial nanobubble nuclei, which are further expanded by rarefaction waves. The rarefaction waves originate from the vibration of the elastic thin walls, which are excited either directly by laser-induced bubble or by bubble-excited liquid-mass oscillations. The oscillation period of thin walls and liquid-mass were Twall = 116 µs and Tlm ≈ 160 µs, respectively. While the amplitude of the wall vibrations increases monotonically with the size of laser-induced bubbles, the amplitude of liquid-mass oscillation undulates with increasing bubble size. This can be attributed to a phase shift between the laser-induced bubble oscillation and the liquid-mass oscillator. Mutual interactions between the laser-induced bubble and secondary bubbles reveal a fast-changing pressure gradient in the liquid. Our study provides a better understanding of laser-induced bubble dynamics in a partially confined environment, which is of practical importance for microfluidics and intraluminal laser surgery.

3.
Int J Mol Sci ; 24(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37108223

RESUMO

Simulated-daylight photodynamic therapy (SD-PDT) may be an efficacious strategy for treating melanoma because it can overcome the severe stinging pain, erythema, and edema experienced during conventional PDT. However, the poor daylight response of existing common photosensitizers leads to unsatisfactory anti-tumor therapeutic effects and limits the development of daylight PDT. Hence, in this study, we utilized Ag nanoparticles to adjust the daylight response of TiO2, acquire efficient photochemical activity, and then enhance the anti-tumor therapeutic effect of SD-PDT on melanoma. The synthesized Ag-doped TiO2 showed an optimal enhanced effect compared to Ag-core TiO2. Doping Ag into TiO2 produced a new shallow acceptor impurity level in the energy band structure, which expanded optical absorption in the range of 400-800 nm, and finally improved the photodamage effect of TiO2 under SD irradiation. Plasmonic near-field distributions were enhanced due to the high refractive index of TiO2 at the Ag-TiO2 interface, and then the amount of light captured by TiO2 was increased to induce the enhanced SD-PDT effect of Ag-core TiO2. Hence, Ag could effectively improve the photochemical activity and SD-PDT effect of TiO2 through the change in the energy band structure. Generally, Ag-doped TiO2 is a promising photosensitizer agent for treating melanoma via SD-PDT.


Assuntos
Melanoma , Nanopartículas Metálicas , Fotoquimioterapia , Humanos , Nanopartículas Metálicas/uso terapêutico , Prata/química , Melanoma/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química
4.
Nanotechnology ; 32(45)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34352746

RESUMO

Purpose. To overcome the insufficiency of conventional photodynamic therapy (PDT) for treating metastatic melanoma, the combination of smart nanoparticles and PDT with immunotherapy was used to achieve a higher efficiency by accumulating more photosensitizers in tumor areas and triggering stronger immune responses against tumors after PDT.Methods. In this study, we designed a nanoliposome co-encapsulation of chlorin E6 (Ce6) and SB-3CT to realize significant antitumoral proliferation and metastasis efficacy after laser irradiation in A375 cells. The morphology, size distribution, and loading efficiency of Ce6-SB3CT@Liposome (Lip-SC) were characterized. The reactive oxygen species (ROS) generation and cytotoxicity were evaluated in A375 cells, and the mechanisms of natural killer (NK) cell-mediated killing were assessed.Results. Lip-SC showed good stability and was well-dispersed with a diameter of approximately 140 nm in phosphate-buffered saline. The nanoliposomes could accumulate in tumor areas and induce apoptosis in cancer cells upon 660 nm light irradiation, which could trigger an immune response and induce the expression of NK group 2 member D (NKG2D) ligands. The subsequently released SB-3CT could further activate NK cells effectively and strengthen the immune system by inhibiting the shedding of soluble NKG2D ligands.Discussion. Taken together, the synergistic effects of SB-3CT on nanoliposomes for Ce6-mediated PDT were analyzed in detail to provide a new platform for future anti-melanoma treatment.


Assuntos
Clorofilídeos/administração & dosagem , Inibidores de Metaloproteinases de Matriz/administração & dosagem , Melanoma/terapia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Fotoquimioterapia/métodos , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Clorofilídeos/química , Clorofilídeos/farmacologia , Feminino , Humanos , Imunoterapia , Células Matadoras Naturais/metabolismo , Lipossomos , Masculino , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Melanoma/metabolismo , Camundongos , Nanopartículas , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Anal Bioanal Chem ; 413(19): 4887-4894, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34100991

RESUMO

Azodicarbonamide (ADA), as a dough conditioner food additive in flour, can be turned into toxic biurea and semicarbazide after high temperature processing. Hence, the using of ADA in food material should be strictly controlled, and the detection of ADA is very important for consumers' safety and health. Herein, a simple and fast colorimetric strategy has been developed for ADA detection based on the MnO2 nanosheets-3,3',5,5'-tetramethylbenzidine (TMB)-glutathione (GSH) as oxidative sensing system (MnO2-TMB-GSH). Since the ADA can selectively react with GSH via oxidizing the sulfydryl (-SH) group of GSH to disulfide bond (S-S), which makes GSH unable to reduce MnO2 nanosheets and restore its oxidase-like activity. The absorbance changes of the TMB solution depended on ADA content. The MnO2-TMB-GSH colorimetric platform can detect the ADA with a linear range of 10 µmol L-1 (11.6 ppm) to 400 µmol L-1 (464 ppm), and the limit of detection (LOD) is 3.3 µmol L-1 (3.51 ppm). Some potential interferences in real sample were tested and did not affect the MnO2-TMB-GSH colorimetric platform for ADA detection. Furthermore, the sensing platform was applied for detecting ADA in real flour sample with a recovery of 96%-105% (RSD < 5%). This colorimetric method can effectively and rapidly detect ADA additives in flour less than the prescribed standard (45 mg kg-1), which shows a great potential for visualization analysis and on-site detection of ADA in flour. A simple and fast colorimetric strategy has been developed for azodicarbonamide (ADA) detection based on the MnO2 nanosheets-3,3',5,5'-tetramethylbenzidine (TMB)-glutathione (GSH) as oxidative sensing system (MnO2-TMB-GSH).

6.
Cytometry A ; 97(1): 31-38, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403260

RESUMO

Pathological diagnosis plays an important role in the diagnosis and treatment of hepatocellular carcinoma (HCC). The traditional method of pathological diagnosis of most cancers requires freezing, slicing, hematoxylin and eosin staining, and manual analysis, limiting the speed of the diagnosis process. In this study, we designed a one-dimensional convolutional neural network to classify the hyperspectral data of HCC sample slices acquired by our hyperspectral imaging system. A weighted loss function was employed to promote the performance of the model. The proposed method allows us to accelerate the diagnosis process of identifying tumor tissues. Our deep learning model achieved good performance on our data set with sensitivity, specificity, and area under receiver operating characteristic curve of 0.871, 0.888, and 0.950, respectively. Meanwhile, our deep learning model outperformed the other machine learning methods assessed on our data set. The proposed method is a potential tool for the label-free and real-time pathologic diagnosis. © 2019 International Society for Advancement of Cytometry.


Assuntos
Carcinoma Hepatocelular/patologia , Aprendizado Profundo , Neoplasias Hepáticas/patologia , Redes Neurais de Computação , Diagnóstico por Computador/métodos , Humanos , Curva ROC
7.
Opt Lett ; 45(13): 3761-3764, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630948

RESUMO

Fluorescence imaging is severely limited by the background and autofluorescence of tissues for in vivo detection of circulating tumor cells (CTCs). Time-gated luminescence (TGL) imaging, in combination with luminescent probes that possess hundreds of microsecond emission lifetimes, can be used to effectively suppress this background, which has predominantly nanosecond lifetimes. This Letter demonstrates the feasibility of TGL imaging using luminescent probes for the in vivo real time imaging and tracking of single CTCs circulating freely in the blood vessels with higher accuracy given by substantially higher signal-to-noise ratio. The luminescent probe used in this Letter was a commercial Eu3+ chelate (EuC) nanosphere with a super-long lifetime of near 800 µs, which enabled TGL imaging to achieve background-free detection with ∼5 times higher SNR versus steady state. Phantom and in vivo mouse studies indicated that EuC labeled tumor cells moving in medium or bloodstream at the speed of 1-2 mm/s could be captured in real time.


Assuntos
Luminescência , Células Neoplásicas Circulantes/patologia , Imagem Óptica/métodos , Análise de Célula Única/métodos , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Razão Sinal-Ruído , Fatores de Tempo
8.
Opt Express ; 26(22): 28560-28575, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30470031

RESUMO

Multiple breakdowns in liquids still remains obscure for its complex, non-equilibrium and transient dynamic process. We introduced three methods, namely, plasma imaging, light-scattering technique, and acoustic detection, to measure the multiple breakdown in water induced by focused nanosecond laser pulses simultaneously. Our results showed that linear dependence existed among the cavitation-bubble lifetime, the far-field peak pressure of the initial shock wave, and the corresponding plasma volume. Such a relationship can be used to evaluate the ideal size and energy of each bubble during multiple breakdown. The major bubble lifetime was hardly affected by the inevitable coalescence of cavitation bubbles, thereby confirming the availability of light-scattering technique on the estimation of bubble size during multiple breakdown. Whereas, the strength of collapse-shock-wave and the subsequent rebound of bubbles was strongly influenced, i.e., the occurrence of multiple breakdown suppressed the cavitation-bubble energy being converted into collapse-shock-wave energy but enhanced conversion into rebound-bubble energy. This study is a valuable contribution to research on the rapid mixing of microfluidics, damage control of microsurgery, and photoacoustic applications.

9.
Analyst ; 144(1): 265-273, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30398232

RESUMO

A conductometric immunoassay protocol was designed for the sensitive detection of a liver cancer biomarker, alpha-fetoprotein (AFP), in biological fluids by using enzyme-conjugated nanometer-sized enzyme-doped silica beads. Initially, urease molecules were doped into nanosilica particles by using the reverse micelle method. Thereafter, arginase-labeled anti-AFP antibodies were covalently conjugated onto the surface of the synthesized nanoparticles. The immunoreaction was carried out in a monoclonal anti-AFP capture antibody-coated microplate with a sandwich-type assay format by using bienzyme-functionalized silica nanobeads as the recognition elements. Upon l-arginine introduction, the substrate was cleaved into urea and l-ornithine on the basis of the arginase enzymatic reaction, and the as-produced urea was then decomposed into ammonia (NH4+) and bicarbonate (HCO3-) ions by the doped urease, thus causing the variation in the local conductivity of the detection solution on an interdigitated conductometric transducer. Under optimal conditions, the developed immunosensing system exhibited good conductometric responses toward target AFP within a dynamic linear range of 0.01-100 ng mL-1 at a relatively low detection limit of 4.8 pg mL-1 based on the 3sB criterion. Importantly, good reproducibility, high specificity and acceptable method accuracy were acquired for the analysis of human serum specimens in liver cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Nanoconjugados/química , Dióxido de Silício/química , alfa-Fetoproteínas/análise , Animais , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/imunologia , Arginase/química , Arginina/química , Biomarcadores Tumorais/imunologia , Canavalia/enzimologia , Bovinos , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Camundongos , Reprodutibilidade dos Testes , Urease/química , alfa-Fetoproteínas/imunologia
10.
Nanotechnology ; 28(25): 255101, 2017 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-28561013

RESUMO

Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle's stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.


Assuntos
Doxorrubicina , Ácido Láctico , Nanopartículas , Neoplasias/tratamento farmacológico , Ácido Poliglicólico , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Hep G2 , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
11.
Nanotechnology ; 28(42): 425102, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28767043

RESUMO

Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.


Assuntos
Doxorrubicina , Glutationa/metabolismo , Hipertermia Induzida/métodos , Micelas , Nanopartículas , Neoplasias , Fototerapia/métodos , Semicondutores , Doxorrubicina/química , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia
12.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 33(6): 1152-7, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29714981

RESUMO

The new mechanisms of automaticity controlled by the calcium and membrane clocks in sinoatrial node are helpful to revealing the sinus arrhythmia,but the present calcium dynamic model is only on the single cell level.In the present study,a central and peripheral single cell model was developed,and by exponentially changing the cell membrane capacitance,size,conductance and gap junction from the center to the periphery,a two-dimensional inhomogeneous sinus and atrial model was created on the basis of the anatomical structure.Five-point difference and finite element methods were used to process the internal grids and the borders.Irregular borders were defined by creating segment trial functions.Quantitative experiments suggested the consistency of the central and peripheral action potentials with related reports in amplitude,cycle length,maximum diastolic potential and upstroke velocity.Functions of the calcium and membrane clocks on the leading pacemaker site and upstroke velocity as well as the effects of the atrial premature beat on the sinus automaticity were also in good agreement with those in other studies.The developed model is helpful for deeply studying relative roles of the calcium and membrane clocks in automaticity and the relations with electrical activities in atrium.At the same time it will lay the foundation for building three-dimensional sinus and atrial organic models.


Assuntos
Arritmia Sinusal/fisiopatologia , Cálcio/fisiologia , Modelos Cardiovasculares , Nó Sinoatrial/fisiologia , Potenciais de Ação , Relógios Biológicos , Diástole , Átrios do Coração , Humanos , Nó Sinoatrial/fisiopatologia
13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 31(2): 462-6, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25039160

RESUMO

This paper provides a brief overview of the current research activities which focused on the bio-application of gold magnetic nanocomposite particles. By combining the magnetic characteristics of the iron oxide core with the unique features of nano-gold particles such as targeting by surface modification and optical properties, such composite nanoparticles have a wide range of applications in cancer hyperthermia, CT and MRI imaging, bio-separation, bio sensors, gene diagnosis, drug targeting and many other biomedical fields.


Assuntos
Ouro/química , Nanocompostos/química , Diagnóstico por Imagem , Sistemas de Liberação de Medicamentos , Compostos Férricos/química , Humanos , Magnetismo , Nanopartículas/química , Neoplasias
14.
Bioact Mater ; 36: 541-550, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39072288

RESUMO

Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy. In addition, application of single mode drug usually leads to unsatisfactory therapeutic outcomes. Currently, developing multimodal-drug combination strategy that acts on different pathways without increasing side effects remains great challenge. Here, we developed a hydrogel system that co-delivered glycolysis inhibitor apigenin and chemo-drug gemcitabine to realize combination strategy for combating cancer with minimal systemic toxicity. We demonstrated that this system can not only eliminate tumor cells in situ, but also induce abscopal effect on various tumor models. These results showed that our study provided a safe and effective strategy for clinical cancer treatment.

15.
Drug Deliv ; 31(1): 2306231, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38245895

RESUMO

Nanosecond pulsed laser induced photoporation has gained increasing attention from scholars as an effective method for delivering the membrane-impermeable extracellular materials into living cells. Compared with femtosecond laser, nanosecond laser has the advantage of high throughput and low costs. It also has a higher delivery efficiency than continuous wave laser. Here, we provide an extensive overview of current status of nanosecond pulsed laser induced photoporation, covering the photoporation mechanism as well as various factors that impact the delivery efficiency of photoporation. Additionally, we discuss various techniques for achieving photoporation, such as direct photoporation, nanoparticles-mediated photoporation and plasmonic substrates mediated photoporation. Among these techniques, nanoparticles-mediated photoporation is the most promising approach for potential clinical application. Studies have already been reported to safely destruct the vitreous opacities in vivo by nanosecond laser induced vapor nanobubble. Finally, we discuss the potential of nanosecond laser induced phototoporation for future clinical applications, particularly in the areas of skin and ophthalmic pathologies. We hope this review can inspire scientists to further improve nanosecond laser induced photoporation and facilitate its eventual clinical application.


Assuntos
Lasers , Nanopartículas , Luz , Pele
16.
Colloids Surf B Biointerfaces ; 242: 114062, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38972255

RESUMO

Pain in photodynamic therapy (PDT), resulting from the stimulation of reactive oxygen species (ROS) and local acute inflammation, is a primary side effect of PDT that often leads to treatment interruption or termination, significantly compromising the efficacy of PDT and posing an enduring challenge for clinical practice. Herein, a ROS-responsive nanomicelle, poly(ethylene glycol)-b-poly(propylene sulphide) (PEG-PPS) encapsulated Ce6 and Lidocaine (LC), (ESCL) was used to address these problems. The tumor preferentially accumulated micelles could realize enhanced PDT effect, as well as in situ quickly release LC due to its ROS generation ability after light irradiation, which owes to the ROS-responsive property of PSS. In addition, PSS can suppress inflammatory pain which is one of the mechanisms of PDT induced pain. High LC-loaded efficiency (94.56 %) owing to the presence of the thioether bond of the PPS made an additional pain relief by inhibiting excessive inflammation besides blocking voltage-gated sodium channels (VGSC). Moreover, the anti-angiogenic effect of LC offers further therapeutic effects of PDT. The in vitro and in vivo anti-tumor results revealed significant PDT efficacy. The signals of the sciatic nerve in mice were measured by electrophysiological study to evaluate the pain relief, results showed that the relative integral area of neural signals in ESCL-treated mice decreased by 49.90 % compared to the micelles without loaded LC. Therefore, our study not only develops a very simple but effective tumor treatment PDT and in situ pain relief strategy during PDT, but also provides a quantitative pain evaluation method.


Assuntos
Lidocaína , Micelas , Fotoquimioterapia , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Lidocaína/farmacologia , Lidocaína/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Dor/tratamento farmacológico , Humanos , Porfirinas/química , Porfirinas/farmacologia , Sulfetos/química , Sulfetos/farmacologia , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Nanopartículas/química , Clorofilídeos
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(5): 1299-303, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23905340

RESUMO

Folate receptor (FR) is particularly upregulated in many epithelial cancer cells membrane and limited distribution is found in normal tissues. In the present work, the folic acid protected gold nanoparticles (FA-GNPs) were synthesized by a simple and quick method, in which chloroauric acid (HAuCl4) was reduced by sodium borohydride (NaBH4) in the presence of FA is used as stabilizer. UV-Visible spectroscopy and transmission electron microscopy (TEM) were used to characterize the shape and size distribution of the produced FA-GNPs. X-ray photoelectron spectroscopy and cell experiment were employed to confirm the immobilization of FA and GNPs. The results showed that FA-GNPs have a good size distribution in the 3-5 nm diameter range. Moreover, it is very stable even in solution with high concentration of salt (up to 3.5% NaCl), and even high speed centrifuges of 25 000 r x min(-1) could not cause aggregation. The nanoparticles could be used to detect cancer cells.


Assuntos
Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ouro/química , Nanopartículas Metálicas/química , Espectroscopia Fotoeletrônica/métodos , Linhagem Celular Tumoral , Humanos , Análise Espectral/métodos
18.
ACS Nano ; 17(15): 14494-14507, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37485850

RESUMO

An immunosuppressive tumor microenvironment (TME) with inadequate and exhausted tumor-infiltrating cytotoxic lymphocytes and abundant cellular immunosuppressors is the major obstacle responsible for the poor efficacy of PD-1/PD-L1 (programmed cell death 1 and its ligand 1) immune checkpoint blockade (ICB) therapy. Herein, a Janus silica nanoparticle (JSNP)-based immunomodulator is explored to reshape the TME for boosting the therapeutic outcomes of αPD-L1 therapy. The designed JSNP has two distinct domains, namely, an ultra pH-responsive side (UPS), which could encapsulate PI3Kγ inhibitor IPI549 in the pore structure, and a polycation-grafted intra-glutathione (GSH)-sensitive side (IGS), which could absorb CXCL9 cDNA on the surface. The final IPI549@UPS-IGS-PDMAEMA@CXCL9 cDNA (IUIPC) could release IPI549 in weak acid TME to target myeloid-derived suppressor cells (MDSCs) to reverse negative immunoregulation and then release CXCL9 cDNA in tumor cells with abundant GSH for sustained CXCL9 chemokine expression and secretion to improve cytotoxic lymphocyte recruitment signals, thereby jointly restoring tumor sensitivity to PD-1/PD-L1 ICB therapy. As expected, the IUIPC-mediated TME remodeling during αPD-L1 therapy significantly ameliorated TME immunosuppression, as well as induced potent systemic antitumor immune responses, which ultimately achieved a robustly boosted antitumor efficacy proven by remarkable suppression of primary tumor growth, obvious prevention of tumor recurrence, and significant regression of abscopal tumors. Hence, the IUIPC-mediated TME-regulating strategy provides an enormous perspective for the improvement of PD-1/PD-L1 ICB therapy.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Antígeno B7-H1 , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Microambiente Tumoral , Receptor de Morte Celular Programada 1 , DNA Complementar , Ligantes , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral
19.
J Biomed Opt ; 28(6): 065006, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37396684

RESUMO

Significance: Resealing time based loading efficiency of optoporation is the key parameter for drug or gene delivery. This work describes a comparatively simple optical approach to directly measure the cell membrane resealing time of the gold nanoparticle mediated photoporation. Aim: To establish a membrane potential detection optical system, which can provide a direct measurement of resealing time of the optoporated cells. Approach: Voltage sensitive dye has been used to label the gold nanoparticle covered cell before laser activation and the resealing time was estimated from the voltage change due to the fluorescence light intensity change before and after laser activation. The approach has been validated by the simulated data based on diffusion model and Monte Carlo simulation and the experimental data obtained from a flow cytometry analysis. Results: The measured resealing time after perforation varied from 28.6 to 163.8 s on Hela cells when the irradiation fluence was increased, with a correlation coefficient (R2) of 0.9938. This result is in agreement with the resealing time (1-2 min) of photothermal porated Hela cells measured by electrical impedance method. The intracellular delivery efficiency of extracellular macromolecular under the same irradiation fluence depends mainly on diffusion velocity rather than pore size. Conclusion: The method described here can be used to directly measure resealing time of optoporated cells for accurately estimating the loading efficiency on discovering the mechanism of optoporation.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Humanos , Células HeLa , Membrana Celular , Preparações Farmacêuticas/metabolismo , Mamíferos
20.
Ultrason Sonochem ; 101: 106664, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37931344

RESUMO

We investigated laser-induced cavitation dynamics in a small container with elastic thin walls and free or partially confined surface both experimentally and by numerical investigations. The cuvette was only 8-25 times larger than the bubble in its center. The liquid surface was either free, or two thirds were confined by a piston-shaped pressure transducer. Different degrees of confinement were realized by filling the liquid up to the transducer surface or to the top of the cuvette. For reference, some experiments were performed in free liquid. We recorded the bubble dynamics simultaneously by high-speed photography, acoustic measurements, and detection of probe beam scattering. Simultaneous single-shot recording of radius-time curves and oscillation times enabled to perform detailed investigations of the bubble dynamics as a function of bubble size, acoustic feedback from the elastic walls, and degree of surface confinement. The bubble dynamics was numerically simulated using a Rayleigh-Plesset model extended by terms describing the acoustically mediated feedback from the bubble's environment. Bubble oscillations were approximately spherical as long as no secondary cavitation by tensile stress occurred. Bubble expansion was always similar to the dynamics in free liquid, and the environment influenced mainly the collapse phase and subsequent oscillations. For large bubbles, strong confinement led to a slight reduction of maximum bubble size and to a pronounced reduction of the oscillation time, and both effects increased with bubble size. The joint action of breakdown-induced shock wave and bubble expansion excites cuvette wall vibrations, which produce alternating pressure waves that are focused onto the bubble. This results in a prolongation of the collapse phase and an enlargement of the second oscillation, or in time-delayed re-oscillations. The details of the bubble dynamics depend in a complex manner on the degree of surface confinement and on bubble size. Numerical simulations of the first bubble oscillation agreed well with experimental data. They suggest that the alternating rarefaction/compression waves from breakdown-induced wall vibrations cause a prolongation of the first oscillation. By contrast, liquid mass movement in the cuvette corners result in wall vibrations causing late re-oscillations. The strong and rich interaction between the bubble and its surroundings may be relevant for a variety of applications such as intraluminal laser surgery and laser-induced cavitation in microfluidics.

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