影像引导在胶质瘤导航手术中的应用与研究进展

胶质瘤的手术切除原则是在保存重要神经功能的前提下尽可能多地切除肿瘤以减少复发率,但术中肉眼识别肿瘤边界较为困难,而影像引导技术在辅助外科胶质瘤手术中通过实时成像有助于保护神经、提高肿瘤切除率和改善病人预后情况。现就CT、MRI、多模态影像技术、荧光影像导航技术、新材料及靶向探针在胶质瘤手术中的临床应用、优势和局限性,以及研究进展进行综述。     

荧光纳米探针在肝癌早期诊疗的研究进展

肝癌的早期诊疗一直是医学领域试图攻克的难题,而纳米技术的发展为肝癌早期诊疗带来新的机遇。目前,荧光纳米探针凭借其良好的靶向性及高敏感度等优势已广泛应用于肝癌成像与诊疗领域。本文将分别从特异性靶向肝癌探针、近红外荧光成像及多模态荧光成像、诊疗一体化三个方面归纳总结荧光纳米探针在肝癌早期诊疗领域的研究进展,提出纳米探针发展亟待解决的问题,并对诊疗一体化纳米体系在肝癌中的应用进行预测。     

分子影像纳米探针在动脉粥样硬化的应用进展

心血管疾病是造成全球疾病负担的主要因素之一,动脉粥样硬化(As)是冠状动脉粥样硬化性心脏病的病理生理学基础,可以长期隐匿存在,直到斑块破裂和血栓形成,进而可导致急性冠状动脉综合征和猝死。如何有效利用影像方法监测As发生发展已成为迫在眉睫的问题。近年来,分子影像技术和纳米医学在As疾病早期诊断中的应用已成为一大热点。本文对纳米医学和分子影像技术在As疾病中的诊断应用进展进行综述。     

Goldmag-based enzyme-linked immunosorbent assay for determination of α-lactalbumin in milk

In this work, a goldmag-based enzyme-linked immunosorbent assay was developed for determination of α-lactalbumin (α-LA) in milk. The magnetic nanoparticle functionalized with polyetherimide was synthesized by one-pot method and coated with two layers of gold nanoparticles on the surface to synthesize goldmag nanoparticles. Anti-α-LA monoclonal antibody, prepared by hybridoma cell lines via cell fusion, was then bound to this goldmag nanoparticle to develop a capture nanoprobe. The results showed that this developed immunoassay had a good linear range of 2.33–127.1?ng/mL with IC₅₀ of 17.2?ng/mL. Besides, recovery rates for α-LA in four commercial milks were from 86.7% to 109.8%. The coefficients of variation in intra-assay and inter-assay were 3.9–6.8% and 5.5–9.8%, separately, which could meet the requirements to quantify α-LA content in milk. This goldmag-based immunoassay might have considerable potentials in the detection of food allergies.     

近红外二区荧光活体成像在细胞示踪上的应用进展

 近红外二区（second near-infrared，NIR-Ⅱ）光因其高组织穿透性及低组织吸收性而得到业内的广泛关注，其荧光成像应用包括血管成像、神经成像、细胞示踪等，其中活体细胞示踪致力于研究细胞的运动轨迹，进而探究体内病理生理过程以寻找治疗方案。肿瘤细胞的示踪可以明确了解其转移并辅助外科手术；干细胞及免疫细胞的示踪可以为细胞治疗法的优化提供有力的依据。本文根据不同的细胞类型进行分类，详细介绍了近年来NIR-Ⅱ荧光成像在细胞示踪上的应用进展，并就现有技术的不足及今后的研究展望展开讨论。     

Synthesis and in vitro evaluation of MR molecular imaging probes using J591 mAb‐conjugated SPIONs for specific detection of prostate cancer

Carcinoma of the prostate is the most frequent diagnosed malignant tumor in men and is the second leading cause of cancer‐related death in this group. The cure rate of prostate cancer is highly dependent on the stage of disease at the diagnosis and early detection is key to designing effective treatment strategies. The objective of the present study is to make a specific MR imaging probe for targeted imaging of cancer cells. We take advantage of the fact that many types of prostate cancer cells express high levels of prostate‐specific membrane antigen (PSMA) on their cell surface. The imaging strategy is to use superparamagnetic iron oxide nanoparticles (SPIONs), attached to an antibody (J591) that binds to the extracellular domain of PSMA, to specifically enhance the contrast of PSMA‐expressing prostate cancer cells. Conjugation of mAb J591 to commercial SPIONs was achieved using a heterobifunctional linker, sulfo‐SMCC. Two types of prostate cancer cell lines were chosen for experiments: LNCaP (PSMA+) and DU145 (PSMA?). MRI and cell uptake experiments demonstrated the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of PSMA‐expressing prostate cancer cells. Copyright © 2012 John Wiley & Sons, Ltd.     

In vivo fluorescence imaging for cancer diagnosis using receptor-targeted epidermal growth factor-based nanoprobe

Receptor-targeted imaging is emerging as a promising strategy for diagnosis of human cancer. Herein, we developed an epidermal growth factor-based nanoprobe (EGF-NP) for in vivo optical imaging of epidermal growth factor receptor (EGFR), an important target for cancer imaging. The self-quenched EGF-NP is fabricated by sequentially conjugating a near-infrared (NIR) fluorophore (Cy5.5) and a quencher (BHQ-3) to EGF, a low-molecular weight polypeptide (6.2 kDa), compared to EGFR antibody (150 kDa). The self-quenched EGF-NP presented great specificity to EGFR, and rapidly internalized into the cells, as monitored by time-lapse imaging. Importantly, the self-quenched EGF-NP boosted strong fluorescence signals upon EGFR-targeted uptake into EGFR-expressing cells, followed by lysosomal degradation, as confirmed by lysosomal marker cell imaging. Consistent with cellular results, intravenous injection of EGF-NP into tumor-bearing mice induced strong NIR fluorescence intensity in the target tumor tissue with high specificity against EGFR-expressing cancer cells. Signal accumulation of EGF-NP in tumor was much faster than that of EGFR monoclonal antibody (Cetuximab)-Cy5.5 conjugates due to the rapid clearance from the body and tissue permeability of low-molecular weight EGF. This self-quenched, EGF-based imaging probe can be applied for diagnosis of various cancers.     

Osteopontin targeted theranostic nanoprobes for laser-induced synergistic regression of vulnerable atherosclerotic plaques

Vulnerable atherosclerotic plaque (VASPs) is the major pathological cause of acute cardiovascular event. Early detection and precise intervention of VASP hold great clinical significance, yet remain a major challenge. Photodynamic therapy (PDT) realizes potent ablation efficacy under precise manipulation of laser irradiation. In this study, we constructed theranostic nanoprobes (NPs), which could precisely regress VASPs through a cascade of synergistic events triggered by local irradiation of lasers under the guidance of fluorescence/MR imaging. The NPs were formulated from human serum albumin (HSA) conjugated with a high affinity-peptide targeting osteopontin (OPN) and encapsulated with photosensitizer IR780 and hypoxia-activatable tirapazamine (TPZ). After intravenous injection into atherosclerotic mice, the OPN-targeted NPs demonstrated high specific accumulation in VASPs due to the overexpression of OPN in activated foamy macrophages in the carotid artery. Under the visible guidance of fluorescence and MR dual-model imaging, the precise near-infrared (NIR) laser irradiation generated massive reactive oxygen species (ROS), which resulted in efficient plaque ablation and amplified hypoxia within VASPs. In response to the elevated hypoxia, the initially inactive TPZ was successively boosted to present potent biological suppression of foamy macrophages. After therapeutic administration of the NPs for 2 weeks, the plaque area and the degree of carotid artery stenosis were markedly reduced. Furthermore, the formulated NPs displayed excellent biocompatibility. In conclusion, the developed HSA-based NPs demonstrated appreciable specific identification ability of VASPs and realized precise synergistic regression of atherosclerosis.     

基于透明质酸的靶向纳米探针的构建及体外抗肿瘤活性

以透明质酸（hyaluronic acid，HA）为药物递送载体，依次连接阿霉素（doxorubicin，DOX）、天然吲哚花青素染料IR808和过氧化氢酶（catalase，CAT），最后通过自组装得到具有抗肿瘤和荧光成像作用的纳米探针CAT@HA-DOX-IR808 NPs。利用紫外可见光分光度计、荧光分光光度计以及透射电子显微镜等对其进行表征，然后在溶液和细胞水平开展其荧光成像和抗肿瘤活性研究。实验结果表明：构建的纳米探针CAT@HA-DOX-IR808为均匀的近球形，尺寸约为75 nm。在pH 5.0和透明质酸酶环境中，DOX在前10 h的释放率达到80%以上。激光共聚焦结果显示，在CD44阳性细胞中，该纳米探针组展现出比游离药物组以及阴性细胞组更显著的荧光信号。细胞毒实验中，在CAT@HA-DOX-IR808 NPs + NIR组，只有大约40%的MDA-MB-231细胞在最高浓度的CAT@HA-DOX-IR808 NPs下存活。因此，纳米探针CAT@HA-DOX-IR808具有显著增强的抗肿瘤功效，在乳腺癌的体外成像和治疗中具有广阔的应用前景。     

同源靶向性多模态成像纳米探针在光热-化疗协同治疗中的应用

目的  制备同源靶向性诊疗一体化纳米探针MnO₂@DOX@ICG@CM(MDIC),观察MDIC纳米探针的同源靶向能力,探讨其多模态成像价值以及光热联合化疗的协同治疗作用。方法  通过化学裂解和超声匀浆法获取乳腺癌4T1细胞膜,以脂质体挤压法制备细胞膜包被的同时载有化疗药阿霉素和光敏剂吲哚菁绿的MnO₂纳米探针;对MDIC的外观形态、粒径和表面电位等性质进行基本表征,并研究其光声成像及磁共振成像的能力;观察不同浓度的MDIC纳米探针的光热升温性能,评估其对4T1细胞的光热-化疗协同治疗的抗肿瘤效果。结果  成功制备MDIC纳米探针,呈花状结构,平均粒径为183.3 nm,表面电位为-20.6±0.77 mV。透射电镜下观察到细胞膜成功包被;MDIC经激光照射后,溶液温度随着纳米探针浓度的升高而增加,具有较好的光热升温效果;光声和磁共振成像结果显示MDIC具有良好的成像对比能力;激光共聚焦显微镜观察到MDIC具有良好的同源靶向性;细胞毒性实验结果显示光热-化疗协同治疗具有更好的癌细胞杀伤作用。结论  本研究成功制备了一种同源靶向性的光声/磁共振多模态成像对比探针MDIC,该探针具有良好的光热升温效能和体外抗肿瘤效果,并且可以显著增强光声成像效果和磁共振T1增强效果。