indocyanine green

吲哚菁绿
  • 文章类型: Journal Article
    吲哚菁绿荧光血管造影术(ICGFA)作为评估皮瓣灌注的术中工具越来越受欢迎。然而,它需要解释,并且担心使用它可能会过度清创。在这里,我们描述了一种人工智能(AI)方法,该方法指示了所需的襟翼修剪程度。
    作为批准的前瞻性研究的一部分,来自10名接受皮瓣重建但没有随后的部分/全部坏死的患者的手术ICGFA记录(NCT04220242,机构审查委员会编号:1/378/2092),提供了训练测试数据集。借鉴ICGFA肠道灌注信号分析的先前类似经验,从稳定的ICGFA图像中分析了五个荧光强度和时间相关特征(MATLABR2024a)。机器学习模型训练(具有十倍交叉验证应用程序)基于ICGFA经验丰富的顾问整形外科医生(S.P.)的实际修剪。MATLAB分类学习器应用程序用于识别最重要的特征,并在训练期间生成可解释性的部分依赖图。测试涉及事后应用于看不到外科医生ICGFA解释的视频。
    训练:测试数据集包括7:3ICGFA视频,分别有28条和3条采样线。验证和测试准确度分别为99.9%和99.3%。最大荧光强度被确定为最重要的预测曲线特征。部分依赖图显示阈值为22.1灰度单位,最大强度小于阈值的区域更有可能被预测为“切除”。
    AI方法在指示是否保留或切除外围皮瓣部分方面被证明是有区别的。需要更多的前瞻性患者和专家参考来验证普遍性。
    UNASSIGNED: Indocyanine green fluorescence angiography (ICGFA) is gaining popularity as an intraoperative tool to assess flap perfusion. However, it needs interpretation and there is concern regarding a potential for over-debridement with its use. Here we describe an artificial intelligence (AI) method that indicates the extent of flap trimming required.
    UNASSIGNED: Operative ICGFA recordings from ten consenting patients undergoing flap reconstruction without subsequent partial/total necrosis as part of an approved prospective study (NCT04220242, Institutional Review Board Ref:1/378/2092), provided the training-testing datasets. Drawing from prior similar experience with ICGFA intestinal perfusion signal analysis, five fluorescence intensity and time-related features were analysed (MATLAB R2024a) from stabilised ICGFA imagery. Machine learning model training (with ten-fold cross-validation application) was grounded on the actual trimming by a consultant plastic surgeon (S.P.) experienced in ICGFA. MATLAB classification learner app was used to identify the most important feature and generate partial dependence plots for interpretability during training. Testing involved post-hoc application to unseen videos blinded to surgeon ICGFA interpretation.
    UNASSIGNED: Training:testing datasets comprised 7:3 ICGFA videos with 28 and 3 sampled lines respectively. Validation and testing accuracy were 99.9 % and 99.3 % respectively. Maximum fluorescence intensity identified as the most important predictive curve feature. Partial dependence plotting revealed a threshold of 22.1 grayscale units and regions with maximum intensity less then threshold being more likely to be predicted as \"excise\".
    UNASSIGNED: The AI method proved discriminative regarding indicating whether to retain or excise peripheral flap portions. Additional prospective patients and expert references are needed to validate generalisability.
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  • 文章类型: Journal Article
    在接受妇科肿瘤外科手术的患者中,降低肠切除术后吻合口漏率是当务之急。虽然近红外(NIR)血管造影术已在结直肠文献中进行了研究,在妇科癌症手术中使用时,最近的研究已经证明了有希望的结果。它已被反复证明是一种安全的干预措施,可以提供实时评估肠灌注,为外科医生提供了对结果采取行动的机会,希望降低并发症的风险。
    Reducing anastomotic leak rates after bowel resection is a priority among patients undergoing gynecologic oncology surgery. While near-infrared (NIR) angiography has been investigated in the colorectal literature, more recent work has demonstrated promising results when used in gynecologic cancer surgery. It has been repeatedly shown to be a safe intervention that can offer real time assessment of bowel perfusion, offering the surgeon the opportunity to act on the results in the hopes of decreasing the risk of complications.
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  • 文章类型: Journal Article
    动脉输入功能(AIF)在校正动脉系统内造影剂的时间依赖性浓度中起着至关重要的作用,考虑药剂注射参数的变化(速度,定时,等。)跨患者。了解AIF的重要性可以通过基于吲哚菁绿的动态对比增强荧光成像(DCE-FI)提高组织血管灌注评估的准确性。
    我们通过DCE-FI评估了AIF对灌注评估的影响。
    使用脉冲染料密度计从110名患者中获得了总共144个AIF。进行模拟和患者术中成像,以基于从AIF校正前后的荧光图像中提取的动力学参数来验证AIF对灌注评估的重要性。通过使用个体AIF与基于群体的AIF评估动力学参数的可变性来评估动力学模型准确性。
    单个AIF可以减少动力学参数的可变性,基于人群的AIF可以替代个体AIF来估计洗脱率(kep),最大强度(Imax),与估计血流量相比,入口斜率差异较小,体积转移常数(Ktrans),是时候达到顶峰了.
    与没有AIF或基于基于人群的AIF校正的评估相比,单独的AIF可以提供最准确的灌注评估。
    UNASSIGNED: The arterial input function (AIF) plays a crucial role in correcting the time-dependent concentration of the contrast agent within the arterial system, accounting for variations in agent injection parameters (speed, timing, etc.) across patients. Understanding the significance of the AIF can enhance the accuracy of tissue vascular perfusion assessment through indocyanine green-based dynamic contrast-enhanced fluorescence imaging (DCE-FI).
    UNASSIGNED: We evaluate the impact of the AIF on perfusion assessment through DCE-FI.
    UNASSIGNED: A total of 144 AIFs were acquired from 110 patients using a pulse dye densitometer. Simulation and patient intraoperative imaging were conducted to validate the significance of AIF for perfusion assessment based on kinetic parameters extracted from fluorescence images before and after AIF correction. The kinetic model accuracy was evaluated by assessing the variability of kinetic parameters using individual AIF versus population-based AIF.
    UNASSIGNED: Individual AIF can reduce the variability in kinetic parameters, and population-based AIF can potentially replace individual AIF for estimating wash-out rate ( k ep ), maximum intensity ( I max ), ingress slope with lower differences compared with those in estimating blood flow, volume transfer constant ( K trans ), and time to peak.
    UNASSIGNED: Individual AIF can provide the most accurate perfusion assessment compared with assessment without AIF or based on population-based AIF correction.
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  • 文章类型: Journal Article
    ALA-PpIX和第二窗口吲哚菁绿(ICG)已被广泛研究,用于指导高级别神经胶质瘤的切除。这些药物具有不同的作用机制和摄取特性,这会影响他们作为手术指导人员的表现。在接近人类大脑的大小和解剖结构的动物模型中阐明这些差异将有助于指导这些药物的使用。在这里,我们报道了使用新的猪神经胶质瘤模型和荧光冷冻成像技术来评估两种药物在整个大脑中的3D分布。
    我们的目标是使用荧光冷冻法评估和比较带有神经胶质瘤的猪脑中ALA-PpIX和第二窗口ICG的3D空间分布。
    通过Cre重组酶质粒的腺相关病毒递送,在转基因Oncopig的大脑中诱导了神经胶质瘤。肿瘤诱导后,在大脑收获前3和24小时对动物施用前体药物5-ALA和ICG,分别。使用荧光冷冻描记术对收获的脑进行成像。使用各种空间分布和对比性能度量在整个大脑中以3D评估两种试剂的荧光分布。
    观察到两种药剂的空间分布的显著差异。吲哚菁绿积聚在肿瘤核心,而ALA-PpIX更多地出现在肿瘤周围。ALA-PpIX和第二窗口ICG均提供升高的肿瘤-背景对比(分别为13和23)。
    这项研究首次证明了使用新的神经胶质瘤模型和大样本荧光冷冻描记术在3D中以高分辨率评估和比较显像剂分布。
    UNASSIGNED: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain.
    UNASSIGNED: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography.
    UNASSIGNED: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics.
    UNASSIGNED: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively).
    UNASSIGNED: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.
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  • 文章类型: Journal Article
    细菌在牙本质小管内的有效消除受到消毒剂的不良沉积和短停留时间的阻碍。同时,当前的冲洗液(例如,NaClO,5.25%)由于其固有的高刺激性,对周围的软组织显示出严重的不良反应。为了解决这个问题,这项工作报告了一种原位产生的超声增敏剂,可以处理牙本质小管中的生物膜,副作用最小。纳米声敏剂的生产涉及H2O2(0.01%)的同时输送,二茂铁衍生物(Fc),和吲哚菁绿(ICG)。用超声波治疗,H2O2与Fc释放的Fe3+之间的反应进一步与ICG复合以原位生成纳米级超声敏化剂,其次是单线态氧的产生,以实现有效的消毒作用。因为上述级联反应发生在狭窄的牙本质小管内,所产生的ICG-Fe3+纳米敏化剂将在其中显示出延长的保留。纳米敏化剂的抗菌效力在petroish和离体生物膜模型中得到证实。同时,生物膜的透射电子显微镜成像和L929成纤维细胞的细胞毒性测定证明了纳米敏化剂对NaClO的不良反应的优越性。目前的工作开辟了牙本质小管生物膜消除的新途径,显示出很高的翻译潜力。
    The efficient elimination of bacteria within the dentinal tubules has been hindered by the poor deposition and short residence of disinfecting agents. Meanwhile, the current irrigant (e.g., NaClO, 5.25 %) shows severe adverse effects on the surrounding soft tissues because of its inherent high irritancy. To address this issue, this work reports an in situ generated sonosensitizer to handle the biofilm in dentinal tubules with minimal adverse effects. The production of nanoscale sonosensitizer involves the concurrent delivery of H2O2 (0.01 %), ferrocene derivative (Fc), and indocyanine green (ICG). With ultrasound treatment, the reaction between H2O2 and Fc liberated Fe3+ that further complexed with ICG to generate the nanoscale sonosensitizer in situ, followed by singlet oxygen production for potent disinfecting action. Because the above cascade reactions occur within the confined dentinal tubules, the generated ICG-Fe3+ nanosensitizer would show prolonged retention therein. The anti-bacterial potency of nanosensitizer was demonstrated in petrodish and ex vivo biofilm models. Meanwhile, the transmission electron microscope imaging of biofilm and cytotoxicity assay in L929 fibroblast cells proved the superiority of nanosensitizer against NaClO regarding adverse effects. The current work opens new avenues of biofilm elimination in dentinal tubules, showing a high translation potential.
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  • 文章类型: Journal Article
    光疗是一种有前途的抗肿瘤方式,其中包括光热疗法(PTT)和光动力疗法(PDT)。然而,肿瘤局部缺氧极大地阻碍了光疗的疗效,吲哚胺2,3-双加氧酶(IDO)和程序性细胞死亡配体-1(PD-L1)在肿瘤细胞上的过表达。为了解决这些问题,自组装多功能聚合物胶束(RIMNA)被开发用于共同递送光敏剂吲哚菁绿(ICG),氧合器MnO2,IDO抑制剂NLG919和toll样受体4激动剂单磷酰脂质A(MPLA)。值得注意的是,RIMNA聚合物胶束具有良好的稳定性,均匀的形态,优越的生物相容性,并加强PTT/PDT效应。更重要的是,RIMNA介导的IDO抑制与程序性死亡受体1(PD-1)/PD-L1阻断相结合,显着改善了免疫抑制并促进了免疫激活。基于RIMNA的光免疫疗法与PD-1抗体协同作用可显著抑制原发肿瘤增殖,以及刺激免疫力,极大地抑制肺转移和远处肿瘤的生长。这项研究提供了一种有效的方法来加强光疗的疗效和减轻免疫抑制,从而为癌症治疗带来临床益处。
    Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What\'s more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.
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  • 文章类型: Journal Article
    患有下肢动脉疾病(LEAD)的患者通常需要进行血运重建手术。目前使用的诊断方法不足以预测成功的结果,并且专注于大血管而不是微血管状态。几种提高诊断准确性的有希望的方式正在出现,包括最大收缩加速度(ACCmax),通过双工超声(DUS)测量。为了评估组织灌注,使用吲哚菁绿(ICG)的近红外荧光(NIR)成像显示了有希望的结果。本研究旨在确定将这两种方法结合用于大血管和微血管灌注评估以预测成功的临床结果的有用性。
    进行了一项回顾性研究,收集了接受血运重建的LEAD患者的介入前和介入后DUS和ICGNIR荧光成像测量值。介入前和介入后灌注参数之间的相关性,描述为δ(Δ)ACCmax和ΔICGNIR荧光参数,进行了分析。灌注参数的改善与临床结果相比,定义为无痛步行距离的改善,从休息的痛苦自由,或倾向于伤口和溃疡愈合。
    共纳入38例患者(42条肢体)。血管重建后ACCmax和ICGNIR荧光灌注参数显著改善(p<0.001)。临床结果差的患者在血运重建后两个参数的改善均显著降低(p<0.001-0.016)。在ACCmax和ICGNIR荧光成像之间发现缺乏相关性。在患者中观察到大血管参数(ACCmax)和灌注(ICGNIR荧光)的多种非一致改善。然而,对于所有临床结果成功的患者,至少一个参数得到改善。
    结合ACCmax和ICGNIR荧光成像显示在具有成功临床结果的所有患者中至少一个参数的改善。这项研究强调了评估下肢血管重建术后大血管状态和组织灌注的潜力,因为两者似乎都反映了血管化的不同方面。
    结论:已经开发了许多技术来评估组织灌注,以预测外周动脉疾病患者血运重建后的临床结果。然而,没有一个在临床实践中广泛实施。这项研究强调了从不同角度采用多种模式进行更准确预测的重要性。通过关注大血管状态和组织灌注,临床医生可以更好地指导自己的治疗策略。
    UNASSIGNED: Patients with lower extremity arterial disease (LEAD) frequently require revascularization procedures. Currently used diagnostic methods are insufficient in predicting successful outcomes and focus on macrovascular rather than microvascular state. Several promising modalities to increase diagnostic accuracy are emerging, including maximal systolic acceleration (ACCmax), measured by duplex ultrasound (DUS). For the assessment of tissue perfusion, near-infrared fluorescence (NIR) imaging using indocyanine green (ICG) demonstrates promising results. This study aims to identify the usefulness of combining these two methods for macrovascular and microvascular perfusion assessment to predict successful clinical outcomes.
    UNASSIGNED: A retrospective study was performed collecting preinterventional and postinterventional DUS and ICG NIR fluorescence imaging measurements from LEAD patients undergoing revascularization. The correlation between the preinterventional and postinterventional perfusion parameters, described as the delta (Δ) ACCmax and ΔICG NIR fluorescence parameters, were analyzed. Improvements in perfusion parameters were compared to clinical outcomes, defined as improvement in pain-free walking distance, freedom from rest pain, or tendency toward wound and ulcer healing.
    UNASSIGNED: A total of 38 patients (42 limbs) were included. ACCmax and ICG NIR fluorescence perfusion parameters improved significantly after revascularization (p<0.001). Patients with a poor clinical outcome had a significantly lower improvement of both parameters after revascularization (p<0.001-0.016). Lack of correlation was found between the delta of ACCmax and ICG NIR fluorescence imaging. Multiple non-congruent improvements of macrovascular parameters (ACCmax) and perfusion (ICG NIR fluorescence) were seen within patients. However, for all patients with a successful clinical outcome, at least one parameter improved.
    UNASSIGNED: Combining ACCmax and ICG NIR fluorescence imaging revealed improvement in at least one parameter within all patients with a successful clinical outcome. This study highlights the potential of assessing both the macrovascular state and tissue perfusion following lower extremity revascularization, as both appear to reflect different aspects of vascularization.
    CONCLUSIONS: Numerous techniques have been developed to assess tissue perfusion to predict clinical outcomes following revascularization in patients with peripheral artery disease. However, none are widely implemented in clinical practice. This study emphasized the importance of employing multiple modalities from different perspectives for more accurate prediction. By focusing on both the macrovascular state and tissue perfusion, clinicians can better guide themselves in their treatment strategies.
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  • 文章类型: Journal Article
    我们评估了预测新生血管性年龄相关性黄斑变性(nAMD)患者一年后视力(VA)的特征。
    共纳入506例患者的527只眼。对机器学习(ML)模型进行了训练,以根据多模态数据的顺序添加,预测1年后超过最小分辨率角度1.0的对数的VA恶化。BaseM模型使用临床数据(年龄,性别,治疗方案,和VA),SegM模型包括来自光学相干断层扫描(OCT)图像的流体体积,RawM模型使用了在基线OCT(OCT0)和三个负荷剂量(OCT3)后训练的深度学习分类器的视力恶化概率(以下简称概率),荧光素血管造影,和吲哚菁绿血管造影.我们将沙普利加法扩张(SHAP)应用于机器学习模型解释。
    基于OCT0概率的RawM模型优于SegM模型(接收器工作特性曲线下的面积为0.95vs.0.91)。加上OCT3,荧光素血管造影,对RawM的吲哚菁绿血管造影显示最小的性能改善,强调使用原始OCT0数据预测视觉结果的实用性。应用SHapley加性移植分析确定3个月后的VA和OCT3概率值是定量流体段上最具影响力的特征。
    集成多模态数据以创建视觉预测模型,可解释的预测。这种方法可以确定预测nAMD患者VA的关键因素。
    从多模态数据中解释nAMD患者1年VA的预测模型使我们能够确定预测VA的关键因素。
    UNASSIGNED: We evaluated the features predicting visual acuity (VA) after one year in neovascular age-related macular degeneration (nAMD) patients.
    UNASSIGNED: A total of 527 eyes of 506 patients were included. Machine learning (ML) models were trained to predict VA deterioration beyond a logarithm of the minimum angle of resolution of 1.0 after 1 year based on the sequential addition of multimodal data. BaseM models used clinical data (age, sex, treatment regimen, and VA), SegM models included fluid volumes from optical coherence tomography (OCT) images, and RawM models used probabilities of visual deterioration (hereafter probability) from deep learning classifiers trained on baseline OCT (OCT0) and OCT after three loading doses (OCT3), fluorescein angiography, and indocyanine green angiography. We applied SHapley Additive exPlanations (SHAP) for machine learning model interpretation.
    UNASSIGNED: The RawM model based on the probability of OCT0 outperformed the SegM model (area under the receiver operating characteristic curve of 0.95 vs. 0.91). Adding probabilities from OCT3, fluorescein angiography, and indocyanine green angiography to RawM showed minimal performance improvement, highlighting the practicality of using raw OCT0 data for predicting visual outcomes. Applied SHapley Additive exPlanations analysis identified VA after 3 months and OCT3 probability values as the most influential features over quantified fluid segments.
    UNASSIGNED: Integrating multimodal data to create a visual predictive model yielded accurate, interpretable predictions. This approach allowed the identification of crucial factors for predicting VA in patients with nAMD.
    UNASSIGNED: Interpreting a predictive model for 1-year VA in patients with nAMD from multimodal data allowed us to identify crucial factors for predicting VA.
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  • 文章类型: Journal Article
    动脉粥样硬化是一种血管内膜疾病,其中循环系统的任何部分都受到影响,包括主动脉和冠状动脉.吲哚菁绿(ICG),一种经FDA批准的治疗药物,在掺入纳米平台后,在治疗冠状动脉粥样硬化方面显示出了希望。通过将ICG与靶向剂(如肽或抗体)整合,增加其在受损动脉中的浓度是可行的,因此增加动脉粥样硬化的检测。Nanotheranosics为动脉粥样硬化斑块的临床诊断和治疗提供了尖端技术。将ICG的光学性质与纳米载体的光学性质组合使得能够改善动脉粥样硬化斑块的成像和靶向治疗干预。已经开发了几种基于ICG的nanotheranosics平台,例如聚合物纳米颗粒,氧化铁纳米颗粒,仿生系统,脂质体,基于肽的系统,等。动脉粥样硬化诊断使用磁共振成像(MRI),计算机断层扫描(CT),近红外荧光(NIRF)成像,光声/超声成像,正电子发射断层扫描(PET),和单光子发射计算机断层扫描(SPECT)成像技术。除了成像,人们对使用ICG治疗动脉粥样硬化越来越感兴趣。在这次审查中,我们为基于ICG的纳米动脉粥样硬化成像和冠状动脉粥样硬化治疗提供了概念性解释.此外,成像模式的进步,如MRI,CT,PET,SPECT,和超声/光声已经被讨论。此外,我们重点介绍了ICG在冠状动脉粥样硬化中的应用.
    Atherosclerosis is a vascular intima condition in which any part of the circulatory system is affected, including the aorta and coronary arteries. Indocyanine green (ICG), a theranostic compound approved by the FDA, has shown promise in the treatment of coronary atherosclerosis after incorporation into nanoplatforms. By integration of ICG with targeting agents such as peptides or antibodies, it is feasible to increase its concentration in damaged arteries, hence increasing atherosclerosis detection. Nanotheranostics offers cutting-edge techniques for the clinical diagnosis and therapy of atherosclerotic plaques. Combining the optical properties of ICG with those of nanocarriers enables the improved imaging of atherosclerotic plaques and targeted therapeutic interventions. Several ICG-based nanotheranostics platforms have been developed such as polymeric nanoparticles, iron oxide nanoparticles, biomimetic systems, liposomes, peptide-based systems, etc. Theranostics for atherosclerosis diagnosis use magnetic resonance imaging (MRI), computed tomography (CT), near-infrared fluorescence (NIRF) imaging, photoacoustic/ultrasound imaging, positron emission tomography (PET), and single photon emission computed tomography (SPECT) imaging techniques. In addition to imaging, there is growing interest in employing ICG to treat atherosclerosis. In this review, we provide a conceptual explanation of ICG-based nanotheranostics for the imaging and therapy of coronary atherosclerosis. Moreover, advancements in imaging modalities such as MRI, CT, PET, SPECT, and ultrasound/photoacoustic have been discussed. Furthermore, we highlight the applications of ICG for coronary atherosclerosis.
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  • 文章类型: Journal Article
    三阴性乳腺癌(TNBC)的特点是复发率和死亡率较高。通过光热疗法(PTT)进行的热介导消融证明了根除乳腺癌的巨大希望。尽管如此,PTT的疗效受到肿瘤细胞热耐受性的阻碍,这归因于热休克蛋白(HSPs)的表达增强。这些蛋白质,作为ATP依赖性分子伴侣,保护癌细胞免受PTT过程中产生的细胞毒性热。糖酵解是乳腺癌细胞产生ATP的重要途径,能促进乳腺癌肺转移的发生和发展。因此,抑制糖酵解可能会减少HSPs的表达,减少乳腺癌的生长,并防止其转移。糖酵解代谢在乳腺癌细胞内的ATP生物合成中起关键作用,促进肺转移的进展和扩散。因此,靶向糖酵解提出了一种HSP表达的战略方法,乳腺癌的增殖,并阻止其转移扩散。在这里,我们设计了一种吲哚菁绿(ICG)和隐丹参酮(CTS)负载透明质酸(HA)的沸石咪唑酯框架-8(ZIF-8)药物递送系统。该给药系统具有优异的光热性能,可以达到足以对肿瘤细胞进行光热消融的温度。(ICG+CTS)@HA-ZIF-8也显示pH响应性药物释放,增强ICG和CTS的持续释放,以延长其体循环持续时间。此外,ZIF-8的HA修饰用于增强其体外和体内靶向能力,利用增强的渗透和保留(EPR)效应,以及通过CD44受体途径主动靶向肿瘤,导致在肿瘤中更高的药物浓度和更好的治疗效果。(ICG+CTS)@HA-ZIF-8下调糖酵解相关蛋白丙酮酸激酶-M2(PKM2)的表达,从而抑制糖酵解过程,进一步抑制肿瘤细胞能量代谢,下调HSPs的表达,克服肿瘤细胞的耐热性,提高PTT效果。它对乳腺癌细胞的增殖和迁移都表现出明显的抑制作用,可能为可视化PTT在乳腺癌治疗中的应用提供创新见解。
    Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.
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