Hyperthermia, Induced

高温, 诱导
  • 文章类型: Journal Article
    微波热疗(MH)期间的实时准确温度监测仍然是确保治疗效果和患者安全的关键挑战。这项研究提出了一种新颖的方法来模拟真实的MH,并使用时间信息神经网络精确确定生物组织内目标区域的温度。我们对30套体模和10套离体猪肉组织进行了MH实验。我们提出了一个新的观点:对连续电磁辐射刺激的组织反应的演变是时间和空间维度的联合演变。我们的模型利用TimesNet提取周期性特征,利用Cloblock从超声图像中捕获二维周期性矢量中的全局信息相关性。通过吸收更多的超声时间数据,我们的模型提高了温度估计的准确性。在25-65°C的温度范围内,我们的神经网络对新鲜离体猪肉组织和体模实现了约0.886°C和0.419°C的温度估计均方根误差,分别。所提出的时间通知神经网络具有适度的参数计数,渲染它适合部署在超声波移动设备。此外,它达到了接近临床标准规定的温度精度,使其在生物组织MH期间的无损温度监测有效。
    Real-time and accurate temperature monitoring during microwave hyperthermia (MH) remains a critical challenge for ensuring treatment efficacy and patient safety. This study presents a novel approach to simulate real MH and precisely determine the temperature of the target region within biological tissues using a temporal-informed neural network. We conducted MH experiments on 30 sets of phantoms and 10 sets of ex vivo pork tissues. We proposed a novel perspective: the evolving tissue responses to continuous electromagnetic radiation stimulation are a joint evolution in temporal and spatial dimensions. Our model leverages TimesNet to extract periodic features and Cloblock to capture global information relevance in two-dimensional periodic vectors from ultrasound images. By assimilating more ultrasound temporal data, our model improves temperature-estimation accuracy. In the temperature range 25-65 °C, our neural network achieved temperature-estimation root mean squared errors of approximately 0.886 °C and 0.419 °C for fresh ex vivo pork tissue and phantoms, respectively. The proposed temporal-informed neural network has a modest parameter count, rendering it suitable for deployment on ultrasound mobile devices. Furthermore, it achieves temperature accuracy close to that prescribed by clinical standards, making it effective for non-destructive temperature monitoring during MH of biological tissues.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    本研究率先采用WIRA全身红外热疗法联合ICI治疗GIT,验证了HIT的可行性和安全性。最终结果显示DCR为55.6%,平均PFS为53.5天,中位OS为134天,IRAE发生率为22.2%。因此,我们认为HIT可以发挥多重协同致敏作用,从而为晚期GIT患者提供临床益处,提高整体安全性,改善患者的生活质量。
    背景:本研究旨在验证有效性,水过滤红外A辐射(WIRA)全身热疗联合免疫检查点抑制剂(ICI)治疗(HIT)的安全性和可行性,并评估真实世界的临床应用前景。
    方法:这项开放标签的单臂2期临床试验(NCT06022692)旨在招募具有MSS/pMMR表型的晚期胃肠道肿瘤(GIT)患者。在每个HIT周期的第1天和第8天对患者进行全身热疗,并在第2天给予tislelizumab。
    结果:在2020年6月1日至2022年5月31日期间,18名患者被纳入研究,包括胃癌患者(n=6),结肠癌(n=7),直肠癌(n=3)和阑尾癌(n=2)。截至2023年5月19日,18名患者中有17人死亡,包括14人因肿瘤进展而死亡,3人因癌症以外的疾病而死亡,而一名患者仍在接受随访。就功效而言,DCR中位数为55.6%,而中位PFS和OS分别为53.5天和134天,分别。四名患者(22.2%)经历了免疫相关的不良事件,没有患者报告3级或更高的irAE。热疗后肿瘤免疫激活细胞数量增加。
    结论:HIT可通过激活抗肿瘤免疫功能为GIT患者提供生存益处,具有良好的安全性和可行性。
    This study pioneered the use of WIRA whole-body infrared hyperthermia combined with ICI therapy to treat GIT and verified the feasibility and safety of HIT. The final results showed a DCR of 55.6%, with a median PFS of 53.5 days, median OS of 134 days, and an irAE incidence of 22.2%. Therefore, we believe that HIT can exert multiple synergistic sensitisation effects, thereby providing clinical benefits to patients with advanced GITs, increasing overall safety, and improving patients\' QOL.
    BACKGROUND: This study aimed to validate the effectiveness, safety and feasibility of water‐filtered infrared A radiation (WIRA) whole‐body hyperthermia combined with immune checkpoint inhibitor (ICI) therapy (HIT) and evaluate the real‐world clinical application prospects.
    METHODS: This open‐label single‐arm phase 2 clinical trial (NCT06022692) aimed to enrol advanced gastrointestinal tumour (GIT) patients with the MSS/pMMR phenotype. The patients were treated with whole‐body hyperthermia on Days 1 and 8 of each HIT cycle along with administration of tislelizumab on Day 2.
    RESULTS: Between 1 June 2020 and 31 May 2022, 18 patients were enrolled in the study, including those with gastric cancer (n = 6), colon cancer (n = 7), rectal cancer (n = 3) and appendiceal cancer (n = 2). As of 19 May 2023, 17 of the 18 patients had died, including 14 deaths caused by tumour progression and three deaths caused by diseases other than cancer, while one patient was still undergoing follow‐up. In terms of efficacy, the median DCR was 55.6%, while the median PFS and OS were 53.5 days and 134 days, respectively. Four patients (22.2%) experienced immune‐related adverse events, and none of the patients reported grade 3 or higher irAEs. Hyperthermia was followed by an increase in the number of tumour immune‐activated cells.
    CONCLUSIONS: HIT can provide survival benefits in patients with GITs by activating antitumour immune function and shows good safety and feasibility.
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  • 文章类型: Journal Article
    体育锻炼对人类健康的益处使得需要确定能够模拟或增强锻炼效果以治疗代谢疾病的新方法。然而,远红外(FIR)热疗是否可以用作运动模拟来实现广泛的代谢调节,其基本机制仍不清楚。这里,基于石墨烯的热疗设备产生的特定远红外(FIR)射线可能会促进运动能力和新陈代谢。材料表征表明,化学气相沉积法(CVD)合成的石墨烯不同于碳纤维,单层结构,电热变换效率高。由石墨烯-FIR装置产生的发射光谱将最大化匹配被组织吸附的那些。石墨烯-FIR提高了核心和表皮温度,导致股肌肉和腹部区域的血流量增加。微生物组学和代谢组学分析的结合表明石墨烯-FIR调节肠-肌肉轴的代谢。这种调节的特征是产生短链脂肪酸(SCFA)的细菌和AMP的丰度增加,而乳酸水平下降。此外,涉及葡萄糖代谢的主要途径,比如糖酵解和糖异生,被发现被改变了。石墨烯-FIR通过激活GPR43设法刺激AMPK活性,从而增强肌肉葡萄糖摄取。此外,微生物群紊乱模型还表明,石墨烯-FIR通过增强p-AMPK和GLUT4有效恢复运动耐力。我们的结果提供了令人信服的证据,表明基于石墨烯的FIR疗法通过肠-肌轴中的AMPK促进运动能力和葡萄糖代谢。这些关于石墨烯-FIR的治疗效果的新发现表明其作为代谢紊乱的临床管理中的模拟剂的潜在效用。
    The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.
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  • 文章类型: English Abstract
    Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m2 of Cisplatin and 30-40 mg/m2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.
    胃癌的腹膜转移与疾病迅速进展相关。细胞减灭术(CRS)后直接进行腹腔热灌注化疗(HIPEC)已成为治疗胃癌腹膜转移患者的重要手段。然而,HIPEC存在不同的治疗方案,如开腹或闭腹、灌注液、管数、温度、持续时间以及不同的药物方案,可影响患者的生存率和预后。本文旨在通过对不同的HIPEC药物技术方案进行系统综述,为HIPEC治疗方案和技术的标准化提供更多参考证据。本文纳入两项随机对照试验、3项Ⅰ和Ⅱ期前瞻性临床试验、两项前瞻性队列研究和34项回顾性队列研究,共1 511例患者。最常见的HIPEC方案为将顺铂50~75 mg/m2和丝裂霉素C 30~40 mg/m2溶解于3~4 L生理盐水中,在42℃~43℃的温度下,胃肠吻合后,于闭腹的HIPEC系统中,使用2~3根导管,灌注液流速为500 ml/min,持续时间为60~90 min。在胃肠吻合后进行HIPEC的研究中,吻合口漏发生率较低。采用开腹HIPEC以及两种药物治疗方案的研究显示总体生存率更高。目前HIPEC的治疗方案存在较大异质性,在临床试验中,需进一步比较技术方法和不同的药物方案,以明确最佳治疗方案,使得该技术合乎标准化。.
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  • 文章类型: Journal Article
    背景:CRS+HIPEC联合泌尿道切除和重建的安全性和有效性存在争议。本研究旨在总结CRS+HIPEC联合泌尿道切除重建的临床病理特征,评价其安全性和生存预后。
    方法:从我们的疾病特异性数据库中回顾性选择作为CRS手术一部分而接受尿路切除和重建的患者进行分析。临床病理特征,治疗相关变量,围手术期不良事件(AE),使用描述性方法和对数秩比较的K-M分析研究了生存结局。
    结果:纳入49例患者。11例(22.4%)患者围手术期出现严重不良事件(SAEs),3例患者发生尿SAE(6.1%)。此外,有23例(46.8%)涉及尿液不良事件(UAE)。整个队列的中位总生存期(OS)为59.2(95CI:42.1-76.4)个月。UAE组和No-UAE组的中位OS为59.2个月(未达到95CI),和50.5(95CI:11.5至89.6)个月,分别,差异无统计学意义(P=0.475)。此外,根据UAE的等级或UAE的数量,OS没有显着差异(分别为P=0.562和P=0.622)。
    结论:CRS+HIPEC与尿路切除和重建的组合与I-II级UAE的高发生率相关,对操作系统没有影响。这种组合技术的安全性是可以接受的。然而,这是一个回顾性的单中心单臂分析,具有普适性和潜在选择偏差的局限性。这些发现需要高级验证。
    BACKGROUND: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction.
    METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison.
    RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively).
    CONCLUSIONS: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.
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  • 文章类型: Journal Article
    纳米粒子介导的热疗研究力求创新,多功能,高效,和安全的治疗。我们的研究引入了一种新颖的纳米平台:聚多巴胺层(HMVNp)内的中空磁性涡旋纳米环,它具有磁性和光热剂的双重功能。利用“双模”方法,将交变磁场(AMF)与近红外(NIR)激光照射相结合,HMVNp显示出加热效率的显着提高(58±8%,SAR=1441对1032W/g),而传统的固体磁铁矿纳米颗粒涂有聚多巴胺(SMNp)。独特的几何形状更大的表面积体积比有利于有效的磁涡旋动力学和增强的热传递。应对耐热热休克蛋白(Hsp)表达的挑战,HMVNp中包封的槲皮素(Q)利用肿瘤酸度和双模式热疗来增强释放,与传统SMNp相比,Q负载能力增加了28.8±6.81%。此外,HMVNp显著提高了磁共振成像(MRI)和光声成像(PAI)的对比度,具有约62%的横向弛豫(R2=81.5vs31.6mM-1s-1[Fe])。体内研究表明,虽然单一治疗减缓了肿瘤的生长,槲皮素双模式治疗可显着减少肿瘤并有效预防转移。我们的研究强调了HMVNp/Q作为热疗干预中通用药物的潜力,提供改进的诊断成像能力。
    Nanoparticle-mediated thermotherapeutic research strives innovative, multifunctional, efficient, and safe treatments. Our study introduces a novel nanoplatform: the hollow magnetic vortex nanorings within a polydopamine layer (HMVNp), which exhibit dual functionality as magnetic and photothermal agents. Utilizing a \"Dual-mode\" approach, combining an alternating magnetic field (AMF) with near-infrared (NIR) laser irradiation, HMVNp demonstrated a significant enhancement in heating efficacy (58 ± 8 %, SAR = 1441 vs 1032 W/g) over traditional solid magnetite nanoparticles coated with polydopamine (SMNp). The unique geometry larger surface area to volume ratio facilitates efficient magnetic vortex dynamics and enhanced heat transfer. Addressing the challenge of heat resistant heat shock protein (Hsp) expression, encapsulated quercetin (Q) within HMVNp leverages tumor acidity and dual-mode thermal therapy to enhance release, showing a 28.8 ± 6.81 % increase in Q loading capacity compared to traditional SMNp. Moreover, HMVNp significantly improves contrast for both magnetic resonance imaging (MRI) and photoacoustic imaging (PAI), with an approximately 62 % transverse relaxation (R2 = 81.5 vs 31.6 mM-1s-1 [Fe]). In vivo studies showed that while single treatments slowed tumor growth, dual-mode therapy with quercetin significantly reduced tumors and effectively prevented metastases. Our study highlights the potential of HMVNp/Q as a versatile agent in thermotherapeutic interventions, offering improved diagnostic imaging capabilities.
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  • 文章类型: Journal Article
    功能性纳米材料与组织工程支架的整合已成为同时治疗恶性骨肿瘤和修复切除的骨缺损的有希望的解决方案。然而,在具有最小化的微结构异质性的3D打印聚合物支架上实现均匀的生物活性界面仍然是一个挑战。在这项研究中,我们报告了一种用于3D打印聚己内酯(PCL)支架的表面工程的简单金属配位自组装策略,该支架具有纳米结构的二维共轭金属有机框架(cMOF),该框架由Cu离子和2,3,6,7,10,11-六羟基三亚苯(HHTP)组成。通过金属离子和HHTP的交替沉积,可以在PCL支架上获得可调厚度的Cu-HHTPcMOF。所得的复合PCL@Cu-HHTP支架不仅表现出有效的OS消融的有效光热转化能力,而且由于其细胞友好的亲水界面而促进了骨修复过程。因此,cMOF设计的双功能3D打印支架通过提供连续的抗肿瘤作用和骨再生能力,显示出治疗骨肿瘤的有希望的潜力。这项工作还为生物活性支架的界面工程提供了一条新途径,以满足骨肉瘤相关骨缺损的多方面需求。
    The integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal-organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). A tunable thickness of Cu-HHTP cMOF on PCL scaffolds was achieved via the alternative deposition of metal ions and HHTP. The resulting composite PCL@Cu-HHTP scaffolds not only demonstrated potent photothermal conversion capability for efficient OS ablation but also promoted the bone repair process by virtue of their cell-friendly hydrophilic interfaces. Therefore, the cMOF-engineered dual-functional 3D-printing scaffolds show promising potential for treating bone tumors by offering sequential anti-tumor effects and bone regeneration capabilities. This work also presents a new avenue for the interface engineering of bioactive scaffolds to meet multifaceted demands in osteosarcoma-related bone defects.
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  • 文章类型: Journal Article
    已显示轻度全身热疗通过免疫调节机制具有抗肿瘤作用。在临床广泛应用之前,在动物中进行大量的机械研究对于坚持循证原则是必要的。基于射频电磁场(RF-EMF)的加热设施可能是热疗治疗的好选择,但是设施的供暖特性,包括结构设计,电磁和热剂量测定,以及热疗的生物学效应,需要很好地阐明。这里,我们报道了由1800MHz固体源激发的谐振腔(RC)的加热特性研究。RC中的EMF由24个静态反射器搅拌,这导致在EM均匀性评估中电场强度的标准偏差低于3dB。对于曝光场景,将6只自由移动的小鼠加载到单独的病例中,并同时暴露在RC中。用数值模拟的12平面波方法计算了暴露小鼠的EMF能量吸收和分布。通过调节源输出功率,可以实现暴露小鼠体内不同水平的核心体温升高。在肝脏中检测到热休克蛋白(HSPs)的过表达,肺和肌肉,但不在暴露小鼠的大脑中。血清中代表性炎性细胞因子的水平,TNF-α和IL-10在RC暴露后增加。在加热特性研究和验证的基础上,所应用的RC将是用于小鼠轻度全身热疗效应研究的合格加热系统。
    轻度全身热疗通过调节免疫系统具有潜在的抗肿瘤作用。基于射频电磁场(RF-EMF)的加热设施成为热疗的合适选择。然而,用于科学研究的合格加热设施必须阐明其加热特性,并验证与热疗相关的生物学效应。在这项研究中,我们报告了使用EMF能量的啮齿动物加热室的特征。腔室的特殊结构不仅实现了有效的EMF使用,而且确保了EMF空间分布的均匀性,动物EM吸收,和EMF引起的生物效应。我们的工作可能会为为科学研究设计低成本但可靠的加热设施提供见解。
    Mild whole-body hyperthermia has been shown to have anti-tumor effects through an immune-modulating mechanism. Before it is widely applied in the clinic, tremendous mechanistic research in animals is necessary to adhere to evidence-based principles. The radio frequency electromagnetic field (RF-EMF) based heating facility could be a good choice for hyperthermia treatment, but the heating characteristics of a facility, including structure design, electromagnetic and thermal dosimetry, and the biologic effects of hyperthermia, need to be well elucidated. Here, we reported the heating characteristic study on a resonant chamber (RC) excited by a 1800 MHz solid source. The EMF in the RC was stirred by 24 static reflectors, which resulted in the standard deviation of electric field intensity being below 3 dB in the EM homogeneity evaluation. For the exposure scenario, six free-moving mice were loaded into separate cases and exposed simultaneously in the RC. The EMF energy absorption and distribution in exposed mice were calculated with the 12-plane-waves method of numerical simulation. Different levels of core body temperature increment in exposed mice were achieved through regulation of the source output power. Overexpression of heat shock proteins (HSPs) was detected in the liver, lung and muscle, but not in the brain of the exposed mice. The levels of representative inflammatory cytokines in the serum, TNF-α and IL-10 increased post RC exposure. Based on the heating characteristic study and validation, the applied RC would be a qualified heating system for mild whole-body hyperthermia effect research in mice.
    Mild whole-body hyperthermia has potential anti-tumor effects by modulating the immune system. A radio frequency electromagnetic field (RF-EMF)-based heating facility emerges as a suitable option for hyperthermia treatment. However, a qualified heating facility for scientific research must elucidate its heating characteristics and validate the biological effects associated with hyperthermia. In this study, we report the characteristics of a rodent heating chamber using EMF energy. The special structure of the chamber not only achieved efficient EMF usage but also ensured the homogeneity in EMF spatial distribution, animal EM absorption, and EMF-caused biological effects. Our work may offer insights for designing a low-cost yet reliable heating facility for scientific research.
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  • 文章类型: Journal Article
    本研究旨在构建靶向载药纳米复合材料(FA-FePt/DDP纳米脂质体),以探索其在卵巢癌治疗和分子磁共振成像(MMRI)中的潜力。
    通过将叶酸(FA)与聚乙二醇(PEG)包覆的铂铁纳米颗粒偶联来制备FA-FePt-NP,并进行表征。然后将顺铂(DDP)封装在FA-FePt-NP中,通过薄膜超声法和高速搅拌合成FA-PEG-FePt/DDP纳米脂质体,其中MMRI的潜力,磁热效应,并对其他涉及的绩效进行了分析。评估了FA-FePt/DDP纳米脂质体联合磁流体热疗(MFH)对卵巢癌的体外和体内治疗作用。检测Bax和上皮间质转化相关蛋白的表达水平。还初步观察到了生物安全性。
    FA-FePt-NP的平均直径约为30nm,FA-FePt/DDP纳米脂质体的水合粒径约为70nm,具有药物缓慢释放和良好的细胞特异性靶向摄取。在交变磁场(AMF)中,FA-FePt/DDP纳米脂质体可迅速达到理想的肿瘤热疗温度(42~44℃)。MRI扫描显示FA-FePt-NPs和FA-FePt/DDP纳米脂质体均能抑制T2信号,表明MMRI具有良好的潜力。体内外实验表明,AMF中的FA-FePt/DDP-NPs可以通过抑制癌细胞增殖来有效抑制卵巢癌的生长,入侵,和移民,诱导癌细胞凋亡,比其他单独疗法好得多;在分子上,E-cadherin和Bax蛋白在卵巢癌细胞和组织中显著升高,而N-钙粘蛋白,Vimentin,Bcl-2蛋白被抑制,有效抑制卵巢癌的恶性进展。此外,在主要脏器中未观察到明显的病理损伤和功能障碍。
    我们成功合成了FA-FePt/DDP纳米脂质体,并证实了它们在AMF和MMRI对卵巢癌的潜力中具有良好的热化疗效果,没有明显的副作用,为卵巢癌的综合靶向治疗和诊断提供了有利的策略。
    UNASSIGNED: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI).
    UNASSIGNED: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed.
    UNASSIGNED: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras.
    UNASSIGNED: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.
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