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1.
Nat Commun ; 12(1): 882, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563996

RESUMO

Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.


Assuntos
Imageamento Tridimensional/métodos , Técnicas Fotoacústicas/métodos , Tomografia Computadorizada por Raios X/métodos , Angiografia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mama/irrigação sanguínea , Mama/diagnóstico por imagem , Desenho de Equipamento , Feminino , Neuroimagem Funcional , Humanos , Imageamento Tridimensional/instrumentação , Técnicas Fotoacústicas/instrumentação , Ratos , Tomografia Computadorizada por Raios X/instrumentação
2.
Nat Commun ; 12(1): 218, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431882

RESUMO

Development of organic theranostic agents that are active in the second near-infrared (NIR-II, 1000-1700 nm) biowindow is of vital significance for treating deep-seated tumors. However, studies on organic NIR-II absorbing agents for photo-to-heat energy-converting theranostics are still rare simply because of tedious synthetic routes to construct extended π systems in the NIR-II region. Herein, we design a convenient strategy to engineer highly stable organic NIR-II absorbing theranostic nanoparticles (Nano-BFF) for effective phototheranostic applications via co-assembling first NIR (NIR-I, 650-1000 nm) absorbing boron difluoride formazanate (BFF) dye with a biocompatible polymer, endowing the Nano-BFF with remarkable theranostic performance in the NIR-II region. In vitro and in vivo investigations validate that Nano-BFF can serve as an efficient theranostic agent to achieve photoacoustic imaging guided deep-tissue photonic hyperthermia in the NIR-II biowindow, achieving dramatic inhibition toward orthotopic hepatocellular carcinoma. This work thus provides an insight into the exploration of versatile organic NIR-II absorbing nanoparticles toward future practical applications.


Assuntos
Temperatura Alta , Raios Infravermelhos , Luz , Compostos Orgânicos/química , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Formazans/administração & dosagem , Formazans/farmacocinética , Camundongos Endogâmicos C57BL , Neoplasias/patologia , Neoplasias/terapia , Técnicas Fotoacústicas
3.
Nat Commun ; 12(1): 34, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397947

RESUMO

Colloidal gold nanoparticles (GNPs) serve as promising contrast agents in photoacoustic (PA) imaging, yet their utility is limited due to their absorption peak in the visible window overlapping with that of hemoglobin. To overcome such limitation, this report describes an ultrapure chain-like gold nanoparticle (CGNP) clusters with a redshift peak wavelength at 650 nm. The synthesized CGNP show an excellent biocompatibility and photostability. These nanoparticles are conjugated with arginine-glycine-aspartic acid (RGD) peptides (CGNP clusters-RGD) and validated in 12 living rabbits to perform multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) for visualization of newly developed blood vessels in the sub-retinal pigment epithelium (RPE) space of the retina, named choroidal neovascularization (CNV). The PAM system can achieve a 3D PAM image via a raster scan of 256 × 256 pixels within a time duration of 65 s. Intravenous injection of CGNP clusters-RGD bound to CNV and resulted in up to a 17-fold increase in PAM signal and 176% increase in OCT signal. Histology indicates that CGNP clusters could disassemble, which may facilitate its clearance from the body.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Microscopia , Imagem Molecular , Técnicas Fotoacústicas , Tomografia de Coerência Óptica , Animais , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/patologia , Meios de Contraste/química , Feminino , Testes de Função Renal , Testes de Função Hepática , Masculino , Nanopartículas Metálicas/ultraestrutura , Camundongos , Oligopeptídeos/química , Coelhos , Distribuição Tecidual
4.
Nat Commun ; 12(1): 716, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514737

RESUMO

For over two decades photoacoustic imaging has been tested clinically, but successful human trials have been limited. To enable quantitative clinical spectroscopy, the fundamental issues of wavelength-dependent fluence variations and inter-wavelength motion must be overcome. Here we propose a real-time, spectroscopic photoacoustic/ultrasound (PAUS) imaging approach using a compact, 1-kHz rate wavelength-tunable laser. Instead of illuminating tissue over a large area, the fiber-optic delivery system surrounding an US array sequentially scans a narrow laser beam, with partial PA image reconstruction for each laser pulse. The final image is then formed by coherently summing partial images. This scheme enables (i) automatic compensation for wavelength-dependent fluence variations in spectroscopic PA imaging and (ii) motion correction of spectroscopic PA frames using US speckle tracking in real-time systems. The 50-Hz video rate PAUS system is demonstrated in vivo using a murine model of labelled drug delivery.


Assuntos
Sistemas Computacionais , Imagem Molecular/métodos , Técnicas Fotoacústicas/métodos , Análise Espectral/métodos , Animais , Desenho de Equipamento , Feminino , Processamento de Imagem Assistida por Computador , Lasers , Camundongos , Camundongos Nus , Modelos Animais , Imagem Molecular/instrumentação , Movimento (Física) , Fibras Ópticas , Imagens de Fantasmas , Técnicas Fotoacústicas/instrumentação , Análise Espectral/instrumentação , Ultrassonografia/instrumentação , Ultrassonografia/métodos
5.
Int J Nanomedicine ; 15: 10199-10213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33364754

RESUMO

Background: Laryngeal cancer is the second most common type of primary epithelial malignant tumor in the head and neck region, and the development of therapies that are more precise, efficient, and safe is necessary to preserve patient speech and swallowing functions as much as possible. Multi-modal imaging-guided photothermal therapy (PTT) can precisely delineate tumors, monitor the real-time accumulation of photothermal agents at the tumor site, accurately select the optimal region for irradiation, and predict the best time for laser treatment. Compared with exogeneous photothermal agents, endogenous melanin materials have better biosafety in vivo, in terms of native biocompatibility and biodegradability, as well as good near-infrared (NIR) absorbance. An NIR-II dye can be attached to melanin via a facile method, and applying a melanin-dye-based nanoprobe could be an excellent choice for the elimination of superficial laryngeal cancer while avoiding total laryngectomy. Methods: In this work, a promising nanoprobe was constructed using a facile EDC/NHS strategy involving an NIR-II dye and melanin nanoparticles. Results: The nanoprobe exhibited good water solubility, dispersibility, strong NIR-II fluorescence and photoacoustic (PA) signals, and higher photothermal performance. Cellular studies showed that the nanoprobe had low toxicity, excellent biocompatibility, and significantly enhanced imaging properties. After the nanoprobe was intravenously injected into Hep-2 laryngeal xenografts, superior dual-modal images were obtained at various time points, which revealed that the optimal photothermal treatment time was 8 h. Subsequently, PTT was carried out in vivo, and laryngeal tumors were completely eliminated after laser irradiation without any obvious side effects. Conclusion: These results indicate the immense potential of nanoprobes for the NIR-II fluorescence/PA imaging-guided photothermal therapy of laryngeal cancer.


Assuntos
Corantes/química , Raios Infravermelhos , Melaninas/síntese química , Nanopartículas/química , Imagem Óptica , Técnicas Fotoacústicas , Animais , Técnicas de Química Sintética , Humanos , Melaninas/química , Nanotecnologia
6.
Int J Nanomedicine ; 15: 10271-10284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33364758

RESUMO

Introduction: Cancer theragnosis involving cancer diagnosis and targeted therapy simultaneously in one integrated system would be a promising solution of cancer treatment. Herein, a convenient and practical cancer theragnosis agent was constructed by combining gold nanocages (AuNCs) covered with selenium and a chitosan (CS) shell (AuNCs/Se) to incorporate the anti-cancer drug doxorubicin (DOX) as a multifunctional targeting nanocomposite (AuNCs/DOX@Se-iRGD) for photoacoustic imaging (PAI)-guided chemo-photothermal synergistic therapy that contributes to enhanced anti-cancer efficacy. The novel design of AuNCs/DOX@Se-iRGD gives the nanocomposite two outstanding properties: (1) AuNCs, with excellent LSPR property in the NIR region, act as a contrast agent for enhanced PAI and photothermal therapy (PTT); (2) Se acts as an anti-cancer nanoagent and drug delivery cargo. Methods: The photothermal performance of these nanocomposites was evaluated in different concentrations with laser powder densities. These nanocomposites were also incubated in pH 5.3, 6.5, 7.4 PBS and NIR laser to study their drug release ability. The cellular uptake was studied by measuring the Se and Au concentrations inside the cells using inductively coupled plasma-mass spectrometry (ICP-MS). Besides, in vitro and in vivo anti-tumor activity were carried out by cytotoxicity assay MTT and tumor model nude mice, respectively. As for imaging, the PA value and images of these nanocomposites accumulated in the tumor site were sequentially collected at specific time points for 48 h. Results and Discussion: The prepared AuNCs/DOX@Se-iRGD showed excellent biocompatibility and physiological stability in different media. In vivo results indicated that the targeting nanocomposite presented the strongest contrast-enhanced PAI signals, which could provide contour and location information of tumor, 24 h after intravenous injection. Likewise, the combined treatment of chemo- and photothermal synergistic therapy significantly inhibited tumor growth when compared with the two treatments carried out separately and showed negligible acute toxicity to the major organs. Conclusion: This study demonstrates that AuNCs/DOX@Se-iRGD has great prospect to become a multifunctional anti-tumor nanosystem for PAI-guided chemo- and photothermal synergistic therapy.


Assuntos
Portadores de Fármacos/química , Ouro/química , Técnicas Fotoacústicas , Selênio/química , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Humanos , Camundongos , Camundongos Nus
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1911-1914, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018375

RESUMO

Photoacoustic imaging has shown its great potential in biomedical imaging. A variety of imaging applications, like blood oxygenation for functional imaging, have been widely studied during the past few decades. Most of the previous works are based on the tissue's endogenous or nanoprobe's extraneous optical absorbance. In this paper, we proposed frequency-domain dual-contrast photoacoustic imaging aiming at exploring both optical absorption and mechanical property (e.g., viscoelasticity) of tissue. Instead of conventionally used pulsed excitation, a chirp-modulated laser signal is used to excite the sample to induce photoacoustic signals. On one hand, the optical absorption contrast is obtained by cross-correlating the PA signals with the chirp pattern. On the other hand, mechanical property is obtained by performing the Fourier transform to analyze the frequency spectrum. Experimental results revealed that samples with higher density-to-viscoelasticity ratio show larger quality factor in the received PA signals' spectrum. Both theoretical analysis and experimental demonstrations are performed to prove the feasibility of the proposed method.


Assuntos
Técnicas Fotoacústicas , Testes Diagnósticos de Rotina , Lasers , Luz , Análise Espectral
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1919-1922, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018377

RESUMO

Photoacoustic imaging which combines high contrast of optical imaging and high resolution of ultrasound imaging, can provide functional information, potentially playing a crucial role in the study of breast cancer diagnostics. However, open source dataset for PA imaging research is insufficient on account of lacking clinical data. To tackle this problem, we propose a method to automatically generate breast numerical model for photoacoustic imaging. The different type of tissues is automatically extracted first by employing deep learning and other methods from mammography. And then the tissues are combined by mathematical set operation to generate a new breast image after being assigned optical and acoustic parameters. Finally, breast numerical model with proper optical and acoustic properties are generated, which are specifically suitable for PA imaging studies, and the experiment results indicate that our method is feasible with high efficiency.


Assuntos
Técnicas Fotoacústicas , Mama/diagnóstico por imagem , Aprendizado Profundo , Humanos , Análise Espectral , Ultrassonografia
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1927-1930, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018379

RESUMO

Skin aging caused by ultraviolet light exposure is one of the serious problems from the viewpoint of beauty and healthcare. This is because ultraviolet light can cause age spot, wrinkles, at the worst case, skin cancer and so on. To evaluate skin aging, various modalities are being used, such as histopathological diagnosis, optical coherence tomography, ultrasound examination (B-mode imaging). However, they have disadvantages in terms of invasiveness, penetration depth and tissue specificity, respectively. To overcome these defects, photoacoustic imaging (PAI), a novel modality was used in this work. This modality can sense differences of tissue characteristics non-invasively. In this experiment, human skin tissues in various generations (i.e. various degrees of photoaging) were measured by using acoustic resolution photoacoustic microscopy (AR-PAM). To verify the feasibility of quantitative skin aging evaluation with PA technique, signals from sectioned human skin (cheek and buttock; female from 28 to 95 years old) were measured with PA microscopy. The effects of photoaging progress on the signal intensity were investigated. The results demonstrated that the PA signal from the dermis significantly increases with aging progress (p < 0.05). These analyses demonstrate the feasibility of quantitative skin aging evaluation with a PAI system.


Assuntos
Técnicas Fotoacústicas , Envelhecimento da Pele , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Microscopia Acústica , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Ultrassonografia
10.
Int J Nanomedicine ; 15: 7687-7702, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116495

RESUMO

Background: Recent studies have validated and confirmed the great potential of nanoscale metal-organic framework (NMOF) in the biomedical field, especially in improving the efficiency of cancer diagnosis and therapy. However, most previous studies only utilized either the metal cluster or the organic ligand of the NMOF for cancer treatments and merely reported limited theranostic functions, which may not be optimized. As a highly designable and easily functionalized material, prospective rational design offers a powerful way to extract the maximum benefit from NMOF for cancer theranostic applications. Materials and Methods: A NMOF based on hafnium (Hf) cluster and Mn(III)-porphyrin ligand was rational designed and synthesized as a high-performance multifunctional theranostic agent. The folic acid (FA) was modified on the NMOF surface to enhance the cancer targeting efficacy. The proposed "all-in-one" FA-Hf-Mn-NMOF (fHMNM) was characterized and identified using various analytical techniques. Then, in vitro and in vivo studies were performed to further explore the effects of fHMNM both as the magnetic resonance imaging (MRI)/computed tomography (CT)/photoacoustic imaging (PAI) contrast agent and as the photothermal therapy (PTT)/radiotherapy (RT) agent. Results: A tumour targeting multifunctional fHMNM was successfully synthesized with high performance for MRI/CT/PAI enhancements and image-guided PTT/RT synergistic therapy properties. Compared with the current clinical CT and MR contrast agents, the X-ray attenuation and T1 relaxation rate of this integrated nanosystem increased 1.7-fold and 3-5-fold, respectively. More importantly, the catalase-like Mn(III)-porphyrin ligand can decompose H2O2 into O2 in tumour microenvironments to improve the synergistic treatment efficiency of PTT and RT. Significant tumour growth inhibition was achieved in mouse cancer models without obvious damage to the other organs. Conclusion: This work highlights the potential of fHMNM as an easily designable material for biomedical applications, could be an effective tool for in vivo detection and subsequent treatment of tumour.


Assuntos
Háfnio/química , Hipertermia Induzida , Estruturas Metalorgânicas/química , Metaloporfirinas/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Animais , Meios de Contraste/química , Fluorescência , Ácido Fólico/uso terapêutico , Células HeLa , Humanos , Imagem por Ressonância Magnética , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Neoplasias/radioterapia , Técnicas Fotoacústicas , Radioterapia Guiada por Imagem
11.
J Vis Exp ; (161)2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32744532

RESUMO

Imaging of vascular networks on small animals has played an important role in basic biomedical research. Photoacoustic imaging technology has great potential for application in the imageology of small animals. The wide-field photoacoustic imaging of small animals can provide images with high spatiotemporal resolution, deep penetration, and multiple contrasts. Also, the real-time photoacoustic imaging system is desirable to observe the hemodynamic activities of small-animal vasculature, which can be used to research the dynamic monitoring of small-animal physiological features. Here, a dual-raster-scanning photoacoustic imager is presented, featuring a switchable double-mode imaging function. The wide-field imaging is driven by a two-dimensional motorized translation stage, while the real-time imaging is realized with galvanometers. By setting different parameters and imaging modes, in vivo visualization of small-animal vascular network can be performed. The real-time imaging can be used to observe pulse change and blood flow change of drug-induced, etc. The wide-field imaging can be used to track the growth change of tumor vasculature. These are easy to be adopted in various areas of basic biomedicine research.


Assuntos
Sistema Cardiovascular/diagnóstico por imagem , Técnicas Fotoacústicas/veterinária , Animais , Técnicas Fotoacústicas/instrumentação
12.
Int J Nanomedicine ; 15: 5687-5700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821097

RESUMO

Background and Purpose: Sonodynamic therapy (SDT) has been widely used for the noninvasive treatment of solid tumors, but the hypoxic tumor microenvironment limits its therapeutic effect. The current methods of reoxygenation to enhance SDT have limitations, prompting reconsideration of the design of therapeutic approaches. Here, we developed a tumor microenvironment-responsive nanoplatform by reducing oxygen consumption to overcome hypoxia-induced resistance to cancer therapy. Methods: A pH-responsive drug-loaded liposome (MI-PEOz-lip) was prepared and used to reduce oxygen consumption, attenuating hypoxia-induced resistance to SDT and thereby improving therapeutic efficiency. Photoacoustic imaging (PAI) and fluorescence imaging (FI) of MI-PEOz-lip were evaluated in vitro and in breast xenograft tumor models. The pH-sensitive functionality of MI-PEOz-lip was applied for pH-triggered cargo release, and its capacity was evaluated. The MI-PEOz-lip-mediated SDT effect was compared with other treatments in vivo. Results: MI-PEOz-lip was demonstrated to specifically accumulate in tumors. Metformin molecules in liposomes selectively accumulate in tumors by pH-responsive drug release to inhibit the mitochondrial respiratory chain while releasing IR780 to the tumor area. These pH-responsive liposomes demonstrated PAI and FI imaging capabilities in vitro and in vivo, providing potential for treatment guidance and monitoring. In particular, the prepared MI-PEOz-lip combined with ultrasound irradiation effectively inhibited breast tumors by producing toxic reactive singlet oxygen species (ROS), while the introduction of metformin inhibited mitochondrial respiration and reduced tumor oxygen consumption, resulting in excellent sonodynamic therapy performance compared with other treatments. Conclusion: In this study, we present a novel strategy to achieve high therapeutic efficacy of SDT by the rational design of multifunctional nanoplatforms. This work provides a new strategy that can solve the current problems of inefficient oxygen delivery strategies and weaken resistance to various oxygen-dependent therapies.


Assuntos
Mitocôndrias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Hipóxia Tumoral , Terapia por Ultrassom , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Respiração Celular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lipossomos , Metformina/farmacologia , Camundongos , Oxigênio/metabolismo , Técnicas Fotoacústicas , Distribuição Tecidual/efeitos dos fármacos , Microambiente Tumoral
13.
Int J Nanomedicine ; 15: 5017-5026, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764933

RESUMO

Background: Molecular imaging is of great benefit to early disease diagnosis and timely treatment. One of the most striking innovations is the development of multimodal molecular imaging technology, which integrates two or more imaging modalities, largely in view of making the best of the advantages of each modality while overcoming their respective shortcomings. Hence, engineering a versatile and easily prepared nanomaterial with integrating multimodal molecular imaging function holds great promise, but is still a great challenge. Materials and Methods: We firstly designed and synthesized a BDT-DPP conjugated polymer and then noncovalent self-assembly with phospholipid-polyethylene glycol endowed BDT-DPP with water solubility and biocompatibility. Followed by [Cu] labeling, the acquired multifunctional nanoparticles (NPs) were studied in detail for the photophysical property. The cytotoxicity and biocompatibility of DPP-BDT NPs were examined through MTT assay and H&E stained analysis. In addition, we investigated the accumulation of the NPs in HepG2 tumor models by positron emission tomography (PET) and photoacoustic (PA) dual-mode imaging. Results and Discussion: The DPP-BDT NPs exhibited excellent optical stability, strong near-infrared (NIR) light absorption as well as fine biocompatibility. After tail vein injection into the living mice, the PA signals in the neoplastic tissues were gradually increased and reached to the maximum at the 4-h post-injection, which was consistent with the PET analysis. Such strong PA and PET signals were attributed to the efficient NPs accumulation resulting from the enhanced permeability and retention (EPR) effect. Conclusion: The biocompatible DPP-BDT NPs demonstrated to be strong NIR absorption property and PAI sensitivity. Besides, these novel DPP-BDT NPs can act not only as a PA imaging contrast agent but also as an imaging agent for PET.


Assuntos
Cetonas/química , Nanopartículas/química , Neoplasias Experimentais/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Tomografia por Emissão de Pósitrons/métodos , Pirróis/química , Animais , Meios de Contraste/química , Radioisótopos de Cobre/administração & dosagem , Radioisótopos de Cobre/farmacocinética , Feminino , Células Hep G2 , Humanos , Injeções , Camundongos , Camundongos Nus , Imagem Multimodal/métodos , Células NIH 3T3 , Nanopartículas/administração & dosagem , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Polímeros/química , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Int J Nanomedicine ; 15: 4151-4169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606670

RESUMO

Purpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement. Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated. Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00±0.1717 nm and an APS-loading efficiency of 54.89±2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo. Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.


Assuntos
Astrágalo (Planta)/química , Neoplasias da Mama/terapia , Ouro/química , Nanopartículas Multifuncionais/química , Nanotubos/química , Polissacarídeos/química , Terapia por Ultrassom , Animais , Antígenos CD/metabolismo , Apoptose , Morte Celular , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/metabolismo , Células Dendríticas/citologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imunoglobulina G/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos BALB C , Fagocitose , Técnicas Fotoacústicas , Poliésteres/síntese química , Poliésteres/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Coelhos , Nanomedicina Teranóstica , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Int J Nanomedicine ; 15: 4289-4309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606678

RESUMO

Objective: To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer. Methods: The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin-avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMA-negative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts. Results: The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately -23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period. Conclusion: The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.


Assuntos
Verde de Indocianina/química , Nanopartículas/química , Imagem Óptica , Técnicas Fotoacústicas , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Fluorescência , Humanos , Masculino , Camundongos Nus , Nanopartículas/ultraestrutura , Tamanho da Partícula , Peptídeos/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/terapia , Ligação Proteica
16.
Int J Nanomedicine ; 15: 4483-4500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606690

RESUMO

Purpose: Tumor metastasis and drug resistance have always been vital aspects to cancer mortality and prognosis. To compromise metastasis and drug resistance, a nanoparticle IPPD-PHF2 (IR780/PLGA-PEI(Dox)-PHF2) has been engineered to accomplish efficient targeted epigenotherapy forced by PHF2-induced MET (mesenchymal to epithelial transition). Materials and Methods: IPPD-PHF2 nanoparticle was synthesized and characterized by several analytical techniques. The transfection efficiency of IPP-PHF2 (IR780/PLGA-PEI-PHF2) was compared with PP-PHF2 (PLGA-PEI-PHF2) in vitro by WB and in vivo by IHC, and the cytotoxicity of IPP was compared with Lipo2000 in vitro by CCK8 assay. The inhibition of cancer cell migration caused by PHF2-upregulation was tested by wound healing assay, and the enhanced chemotherapeutic sensitivity was detected by flow cytometry. Tumor-targeting property of IPPD-PHF2 was proved by fluorescent imaging in vivo with MDA-MB-231 tumor-bearing nude mice. Except for fluorescent imaging ability, considerable photoacoustic signals of IPPD-PHF2 at tumor sites were verified. The anti-tumor activity of IPPD-PHF2 was investigated using in vivo human breast cancer MDA-MB-231 cell models. Results: Tumor-targeting nanoparticle IPPD-PHF2 had an average size of about 319.2 nm, a stable zeta potential at about 38 mV. The encapsulation efficiency of doxorubicin was around 39.28%, and the adsorption capacity of plasmids was about 64.804 µg/mg. Significant up-regulation of PHF2 induced MET and caused reduced migration as well as enhanced chemotherapeutic sensitivity. Either IPPD (IR780/PLGA-PEI(Dox)) or IPP-PHF2 (IR780/PLGA-PEI-PHF2) presented minor therapeutic effects, whereas IPPD-PHF2 specifically accumulated within tumors, showed extraordinary transfection efficiency specifically in tumor sites, acted as inhibitors of metastasis and proliferation, and presented good multimodality imaging potentials in vivo. Conclusion: IPPD-PHF2 NPs is a promising tool to bring epigenotherapy into a more practical era, and the potential application of harm-free multimodality imaging guidance is of great value.


Assuntos
Antineoplásicos/uso terapêutico , Epigênese Genética , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transfecção , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Indóis/química , Camundongos Nus , Nanopartículas/ultraestrutura , Metástase Neoplásica , Técnicas Fotoacústicas , Polietilenoimina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química
17.
Recent Results Cancer Res ; 216: 155-187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32594387

RESUMO

The present chapter summarizes progress with optical methods that go beyond human vision. The focus is on two particular technologies: fluorescence molecular imaging and optoacoustic (photoacoustic) imaging. The rationale for the selection of these two methods is that in contrast to optical microscopy techniques, both fluorescence and optoacoustic imaging can achieve large fields of view, i.e., spanning several centimeters in two or three dimensions. Such fields of views relate better to human vision and can visualize large parts of tissue, a necessary premise for clinical detection. Conversely, optical microscopy methods only scan millimeter-sized dimensions or smaller. With such operational capacity, optical microscopy methods need to be guided by another visualization technique in order to scan a very specific area in tissue and typically only provide superficial measurements, i.e., information from depths that are of the order of 0.05-1 mm. This practice has generally limited their clinical applicability to some niche applications, such as optical coherence tomography of the retina. On the other hand, fluorescence molecular imaging and optoacoustic imaging emerge as more global optical imaging methods with wide applications in surgery, endoscopy, and non-invasive clinical imaging, as summarized in the following. The current progress in this field is based on a volume of recent review and other literature that highlights key advances achieved in technology and biomedical applications. Context and figures from references from the authors of this chapter have been used here, as it reflects our general view of the current status of the field.


Assuntos
Imagem Molecular , Técnicas Fotoacústicas , Humanos
18.
Recent Results Cancer Res ; 216: 337-355, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32594392

RESUMO

Tissue has characteristic properties when it comes to light absorption and scattering. For optical (OI) and optoacoustic imaging (OAI) these properties can be utilised to visualise biological tissue characteristics, as, for example, the oxygenation state of haemoglobin alters the optical and optoacoustic properties of the molecule.


Assuntos
Técnicas Fotoacústicas , Humanos
19.
Recent Results Cancer Res ; 216: 439-492, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32594395

RESUMO

The spatiotemporal determination of molecular events and cells is important for understanding disease processes, especially in oncology, and thus for the development of novel treatments. Equally important is the knowledge of the biodistribution, localization, and targeted accumulation of novel therapies as well as monitoring of tumor growth and therapeutic response. Optical imaging provides an ideal versatile platform for imaging of all these problems and questions.


Assuntos
Neoplasias/diagnóstico por imagem , Técnicas Fotoacústicas , Humanos , Oncologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Distribuição Tecidual
20.
Int J Comput Assist Radiol Surg ; 15(6): 1053-1062, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32451814

RESUMO

PURPOSE: A real-time intra-operative imaging modality is required to update the navigation systems during neurosurgery, since precise localization and safe maximal resection of gliomas are of utmost clinical importance. Different intra-operative imaging modalities have been proposed to delineate the resection borders, each with advantages and disadvantages. This preliminary study was designed to simulate the photoacoustic imaging (PAI) to illustrate the brain tumor margin vessels for safe maximal resection of glioma. METHODS: In this study, light emitting diode (LED)-based PAI was selected because of its lower cost, compact size and ease of use. We developed a simulation framework based on multi-wavelength LED-based PAI to further facilitate PAI during neurosurgery. This framework considers a multilayer model of the tumoral and normal brain tissue. The simulation of the optical fluence and absorption map in tissue at different depths was computed by Monte Carlo. Then, the propagation of initial photoacoustic pressure was simulated by using k-wave toolbox. RESULTS: To evaluate the LED-based PAI, we used three evaluation criteria: signal-to-noise ratio (SNR), contrast ratio (CR) and full width of half maximum (FWHM). Results showed that by using proper wavelengths, the vessels were recovered with the same axial and lateral FWHM. Furthermore, by increasing the wavelength from 532 to 1064 nm, SNR and CR were increased in the deep region. The results showed that vessels with larger diameters at same wavelength have a higher CR with average improvement 28%. CONCLUSION: Multi-wavelength LED-based PAI provides detailed images of the blood vessels which are crucial for detection of the residual glioma: The longer wavelengths like 1064 nm can be used for the deeper tumor margins, and the shorter wavelengths like 532 nm for tumor margins closer to the surface. LED-based PAI may be considered as a promising intra-operative imaging modality to delineate tumor margins.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Encéfalo/patologia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Técnicas Fotoacústicas/métodos , Algoritmos , Simulação por Computador , Meios de Contraste , Humanos , Processamento de Imagem Assistida por Computador , Período Intraoperatório , Luz , Margens de Excisão , Modelos Teóricos , Método de Monte Carlo , Fótons , Estudo de Prova de Conceito , Razão Sinal-Ruído , Análise Espectral , Cirurgia Assistida por Computador
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