Interactions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications

Although considerable efforts have been conducted to diagnose, improve, and treat cancer in the past few decades, existing therapeutic options are insufficient, as mortality and morbidity rates remain high. Perhaps the best hope for substantial improvement lies in early detection. Recent advances in nanotechnology are expected to increase the current understanding of tumor biology, and will allow nanomaterials to be used for targeting and imaging both in vitro and in vivo experimental models. Owing to their intrinsic physicochemical characteristics, nanostructures (NSs) are valuable tools that have received much attention in nanoimaging. Consequently, rationally designed NSs have been successfully employed in cancer imaging for targeting cancer‐specific or cancer‐associated molecules and pathways. This review categorizes imaging and targeting approaches according to cancer type, and also highlights some new safe approaches involving membrane‐coated nanoparticles, tumor cell‐derived extracellular vesicles, circulating tumor cells, cell‐free DNAs, and cancer stem cells in the hope of developing more precise targeting and multifunctional nanotechnology‐based imaging probes in the future.     

High‐Security Nanocluster for Switching Photodynamic Combining Photothermal and Acid‐Induced Drug Compliance Therapy Guided by Multimodal Active‐Targeting Imaging

High‐security nanoplatform with enhanced therapy compliance is extremely promising for tumor. Herein, using a simple and high‐efficient self‐assembly method, a novel active‐targeting nanocluster probe, namely, Ag₂S/chlorin e6 (Ce6)/DOX@DSPE‐mPEG₂₀₀₀‐folate (ACD‐FA) is synthesized. Experiments indicate that ACD‐FA is capable of specifically labeling tumor and guiding targeting ablation of the tumor via precise positioning from fluorescence and photoacoustic imaging. Importantly, the probe is endowed with a photodynamic “on‐off” effect, that is, Ag₂S could effectively quench the fluorescence of chlorin e6 (89.5%) and inhibit release of ¹O₂ (92.7%), which is conducive to avoid unwanted phototoxicity during transhipment in the body, and only after nanocluster endocytosed by tumor cells could release Ce6 to produce ¹O₂. Moreover, ACD‐FA also achieves excellent acid‐responsive drug release, and exhibits eminent chemo‐photothermal and photodynamic effects upon laser irradiation. Compared with single or two treatment combining modalities, ACD‐FA could provide the best cancer therapeutic effect with a relatively low dose, because it made the most of combined effect from chemo‐photothermal and controlled photodynamic therapy, and significantly improves the drug compliance. Besides, the active‐targeting nanocluster notably reduces nonspecific toxicity of both doxorubicin and chlorin e6. Together, this study demonstrates the potency of a newly designed nanocluster for nonradioactive concomitant therapy with precise tumor‐targeting capability.     

距离选通水下激光成像系统设计及实验

针对浅水目标探测这一难题,设计了一种基于距离选通技术的水下成像系统。系统围绕532nm Nd…YAG脉冲激光器和选通式增强型电荷耦合器件(ICCD)摄像机搭建而成,并且采用激光脉冲作为系统同步控制的触发信号。采用基于现场可编程门阵列(FPGA)技术设计的同步控制电路,进行了距离选通水下激光成像实验。实验结果表明,采用激光脉冲触发同步控制电路的方法,可有效抑制激光脉冲抖动对系统同步控制精度的影响,从而克服水体表面反射和后向散射对成像的影响,提高了成像质量。在有效衰减系数为0.52m-1的湖泊中,系统的成像深度可达到水下7m,对于浅水目标的探测、识别非常有效。     

主动式毫米波成像系统实现与方案设计

针对被动式毫米波成像信号强度弱,成像实际效果差,成像速度慢、设备体积大等缺点,本文通过对主动毫米波成像算法的分析,利用35GHz毫米波,设计并实现了一套单点式近场主动毫米波成像系统,扫描一个人体全身像时间为200s,分辨率为10.5mm,体积小于1.5m3,进而提出了一个改进的阵列式毫米波成像系统方案,其扫描一个人体像的速度达到了38.7s,分辨率达3.225cm。该主动式毫米波成像系统扫描的实际效果也较为理想,对于人体上的刀具等分辨清晰。     

Ka 波段主动成像宽带收发前端的研制

以毫米波成像应用为背景,研制了一种用于Ka波段主动成像系统的宽带收发前端。采用结构紧凑的自差式结构,降低系统成本并使其具有较高的可靠性;分析影响成像系统的动态范围和分辨率的因素,选择并设计宽频带毫米波源、低插损带通滤波器和平面缝隙天线等关键电路,使前端具有足够的输出功率和良好的杂散抑制,在31～36GHz的频带内,收发前端的输出功率大于10.4dBm,杂散抑制大于25dBc。对金属目标的成像实验结果表明,前端的方位向和距离向的分辨能力小于8cm,初步满足了主动成像的要求。     

医疗内窥镜影像系统的设计与实现

设计并实现了消化内镜影像系统的常用功能,并增加了病变图像的二次采集,典型病例库的维护以及“所见即所得”的报告生成方式,提高了诊断效率。并对系统进行了全面的测试,保证了系统的稳定性和功能完备性。     

Targeted Tumor Hypoxia Dual‐Mode CT/MR Imaging and Enhanced Radiation Therapy Using Dendrimer‐Based Nanosensitizers

The efficacy of radiation therapy (RT) is often limited by the poor response of hypoxia inside most solid tumors. The development of a theranostic nanoplatform for precision‐imaging‐guided sensitized RT for tumor hypoxia is still challenging. Herein, the creation of hypoxia‐targeted dendrimer‐entrapped gold nanoparticles complexed with gadolinium(III) (Gd‐Au DENPs‐Nit) for dual‐mode CT/MR imaging and sensitized RT of hypoxic tumors is reported. In this work, generation 5 poly(amidoamine) dendrimers are partially conjugated with Gd(III) chelator, entrapped with Au nanoparticles, and conjugated with hypoxia‐targeting agent nitroimidazole via a polyethylene glycol linker, and ending with chelation of Gd(III) and conversion of their leftover amine termini to acetamides. The designed dendrimer‐based nanohybrids with 3.2 nm Au cores exhibit an excellent X‐ray attenuation effect, acceptable r₁ relaxivity (1.32 mM^?1 s^?1), and enhanced cellular uptake in hypoxic cancer cells, affording efficient dual‐mode CT/MR imaging of tumor hypoxia. Under X‐ray irradiation, the Gd‐Au DENPs‐Nit nanohybrids can produce reactive oxygen species, promote DNA damage, and prevent DNA repair, facilitating sensitized RT of hypoxic cancer cells in vitro and tumor hypoxia in vivo. The developed hypoxia‐targeted dendrimer‐based nanohybrids may be employed as both contrast agents and nanosensitizers for precision tumor hypoxia imaging and sensitized tumor RT.     

Gold Nanoclusters‐Based Nanoprobes for Simultaneous Fluorescence Imaging and Targeted Photodynamic Therapy with Superior Penetration and Retention Behavior in Tumors

Gold nanoclusters (GNCs) attract increasing attention due to their potential applications in sensing, catalysis, optoelectronics, and biomedicine. Herein, the formation of highly fluorescent glutathione (GSH)‐capped GNCs is achieved through the delicate control of the reduction kinetics and thermodynamic selection of the Au(I)–SG complexes. Furthermore, the GNCs‐based nanoprobes are developed by the covalent coupling folic acid (FA) and PEG (polyethylene glycol) on the surface of GNCs directly, followed by trapping photosensitizer (chlorin e6, Ce6) within PEG networks and attaching to the GNCs surface. The fabricated nanoprobes (Ce6@GNCs‐PEG_2K‐FA) possess a uniform particle size (hydrodynamic diameter ≈6.1 ± 1.2 nm), without affecting the yield of singlet oxygen of the trapped Ce6. In vitro studies show the enhanced cellular uptake and satisfactory photodynamic therapy (PDT) effectiveness toward MGC‐803 cells when compared with free Ce6. The biodistribution and excretion pathway studies of the nanoprobes in MGC‐803 tumor‐bearing nude mice reveal their superior penetration and retention behavior in tumors, while the preserved features of renal clearance and stealthy to reticulo‐endothelial system are mainly attributed to the small hydrodynamic diameters and the FA‐capped PEGylated ligands. The enhanced PDT efficacy and the nontoxicity to mice provide an exciting new nano‐platform with promising clinical translational potential.     

利用激光散斑成像监测光动力治疗的血管损伤效应

激光散斑衬比成像(LSCI)技术作为一种高时空分辨的血流流速分布监测技术，无需扫描即可实时地全场记录微循环血流的时空变化特性。鸡胚尿囊膜(CAM)是用于在体研究光动力治疗(PDT)血管损伤效应的理想动物模型。以发育10天鸡胚尿囊膜为模型，使用光敏剂——焦脱镁叶绿酸(pyropheophorbide acid，pyro-acid)，激光照射波长为656．5nm，光照射功率为40mW／cm^2，研究了肿瘤周围血管在激光照射下的血管管径变化和血流速度分布变化。研究表明，通过对血管管径和血流速度的监测，激光散斑衬比成像技术可以用于评估光动力治疗过程中的肿瘤周围血管损伤效应。     

Nucleus‐Targeting Gold Nanoclusters for Simultaneous In Vivo Fluorescence Imaging,Gene Delivery,and NIR‐Light Activated Photodynamic Therapy

The nucleus is one of the most important cellular organelles and molecular anticancer drugs, such as cisplatin and doxorubicin, that target DNA inside the nucleus, are proving to be more effective at killing cancer cells than those targeting at cytoplasm. Nucleus‐targeting nanomaterials are very rare. It is a grand challenge to design highly efficient nucleus‐targeting multifunctional nanomaterials that are able to perform simultaneous bioimaging and therapy for the destruction of cancer cells. Here, unique nucleus‐targeting gold nanoclusters (TAT peptide–Au NCs) are designed to perform simultaneous in vitro and in vivo fluorescence imaging, gene delivery, and near‐infrared (NIR) light activated photodynamic therapy for effective cancer cell killing. Confocal laser scanning microscopy observations reveal that TAT peptide–Au NCs are distributed throughout the cytoplasm region with a significant fraction entering into the nucleus. The TAT peptide–Au NCs can also act as DNA nanocargoes to achieve very high gene transfection efficiencies (≈81%) in HeLa cells and in zebrafish. Furthermore, TAT peptide–Au NCs are also able to sensitize formation of singlet oxygen (¹O₂) without the co‐presence of organic photosensitizers for the destruction of cancer cells upon NIR light photoexcitation.     

Squaraine Dyes for Photovoltaic and Biomedical Applications

Squaraine dyes (SQs) are an important class of polymethine dyes with a unique reasonable-stabilized zwitterionic structure, in which electrons are highly delocalized over the conjugated bridge. These dyes can not only be easily synthesized via a condensation, but also exhibit intense absorption and emission in the visible and near-infrared region with excellent photochemical stability, making them attractive material candidates for many photoelectric and biomedical applications. Thus, in this review, after an introduction of SQs, the recent advances of SQs in the photovoltaic field are comprehensively summarized including dye-sensitized solar cells, organic solar cells, and perovskite solar cells. Then, the important advances in the use of SQs as the biosensors, biological imaging, and photodynamic/photothermal therapy reagents in the biomedical field are also discussed. Finally, a summary and outlook will be provided with some new perspectives for the future design of SQs.     

Targeted Magnetic Resonance Imaging/Near-Infrared Dual-Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

Accurate identification and visualization of peritoneal metastases (PM) are clinically essential to improving the prognosis for gastric cancer. However, owing to the multifocal spread of peritoneal metastasis nodules, small size, and close contact with adjacent organs, identifying and completely removing them during surgery is extremely challenging, resulting in cancer treatment failure and recurrence. This study develops a T₁-weighted magnetic resonance imaging (MRI) contrast agent (FeGdNP)-loaded indocyanine green/glucose oxidase (ICG/GOx) with conjugation of an RGD dimer (RGD2) and acid-labile polymer mPEG (FeGdNP-ICG/GOx-RGD2-mPEG). Compared with commercial Magnevist, the proposed FeGdNP-ICG/GOx-RGD2-mPEG shows a two to three-fold higher tumor ΔSNR in MRI of peritoneal metastasis and subcutaneous animal models. Compared with free ICG, the increased fluorescent signal of FeGdNP-ICG/GOx-RGD2-mPEG allows for the detection of tiny tumor metastatic nodules (<3 mm), and the removal of the peritoneum transplanted tumors. Abundant gluconic acid and H₂O₂ are generated during the GOx-mediated glucose depletion process in cancer cells, thereby enhancing Fenton reaction efficiency. Accumulated toxic ·OH can damage the mitochondrial function and induce the release of mitochondrial reactive oxygen species, which activates the ferroptosis pathway. The data indicate the potential of the nanoparticles for MRI preoperative diagnosis, intraoperative fluorescence-guided navigation, and ferroptosis tumor therapy.     

先进合成孔径雷达/逆合成孔径雷达成像及其特征分析

叙述了先进合成孔径雷达／逆合成孔径雷达成像法和超分辨问题。文中的机载SAR用一发三收四口径天线对地面动目标进行监测和跟踪。简单讨论了ISAR的极坐标重组、现代谱分析和时一频成像法。