金纳米棒的光学性质及其在癌症诊断和光热疗法中的应用

与球形金颗粒相比,棒状金颗粒具有更为特殊的表面等离子共振(SPR)特性:有横向和纵向两个SPR峰,纵向SPR峰的位置取决于金纳米棒颗粒的长短轴比,因此通过控制不同长短轴比,可以实现纵向SPR峰位置的人为调控(从可见光区到近红外光区),金纳米棒,由于其表面SPR等强吸收和发光特性,在癌症的诊断和治疗中存在着巨大的应用前景.结合配体的金纳米棒能够特异性地标记癌症细胞上的受体,并提供特定分子的特有信息,进行生物成像和癌症检测.另外,金纳米棒能够有效地吸收红外光能量进行局部加热,导致蛋白质变性,并致细胞死亡.主要回顾各种不同尺寸和形状的金纳米棒的光学特性,综述了选择性标记的金纳米棒在癌症诊断和光热疗法中的研究进展.     

光纤型光学相干层析技术系统的眼科成像

建立了一套单模光纤型光学相干层析(OCT)成像系统,开展了动物眼睛的成像实验,实现了高信噪比、高分辨率、大成像深度的层析图像的获取.系统纵向分辨率达到9μm,横向分辨率为10μm,最大层析成像深度可达3.4 mm.实验图像和商业蔡氏三代光学相干层析技术成像的对比结果表明,研制的OCT系统已经能展示视网膜的基本分层结构,而且能分辨脉络膜的分层结构和脉络膜血管,后者是蔡氏三代OCT系统所无法实现的.     

不同尺寸、形状和组成的金纳米颗粒的光热特性:在癌症治疗中的应用

光热疗法由于其安全和高效的优点,作为一种非破坏性方法在癌症治疗中有广泛的应用前景。光热疗法中,所采用的纳米颗粒在近红外波段的光热转换效率取决于纳米颗粒的光谱吸收特性。采用时域有限差分法对球型、壳型、杆型、片型、笼型、星型和花型等七种不同金纳米颗粒的光谱吸收特性进行了仿真计算,结果表明纳米颗粒的几何参数和结构对其光谱吸收效率和共振波长产生了显著的影响。通过对比七种金纳米颗粒的体积吸收系数,发现金纳米片在近红外波段的光热转换效率优于其他六种金纳米颗粒。从电流密度矢量分布得出,金纳米颗粒内部产生共振电流是导致金纳米颗粒在近红外波段具有明显的单色吸收特性的原因。     

双金属ZnAu纳米团簇的光学性质及生物成像应用

为了优化Au纳米团簇(nanoclusters,NCs)的光 学性能,拓宽它的应用领域,利用原子掺杂法合成 了超稳定的发光双金属ZnAu NCs。通过对紫外-可见吸收光谱、发射光谱、红外光谱、荧光 寿命等的测试 和分析,研究了合成的ZnAu NCs的光学特性,讨论了Zn原子掺杂对Au NCs发光性能的影响, 并且借 助透射电子显微镜和质谱等表征手段,分析了这种光学材料的结构性质。最后,通过细胞毒 性评估以及细 胞成像实验探究了其在生物医学上的应用。研究结果表明,与未掺杂原子的Au NCs相比,掺 杂Zn原子的 ZnAu NCs的荧光强度增强了3倍左右,荧光寿命也从6.73 μs延长到 7.26 μs。此外,结合 质谱确定了超小 的ZnAu NCs是分子量位于5.0 kDa－5.8 kDa之 间的复合物团簇。这种发光纳米材料所表现出的良好的光稳 定性和低细胞毒性,使其在生物成像领域具有潜在的应用价值。同时,Zn原子的掺杂提升了 Au NCs的光学性能,为其在其它领域的广泛应用提供了更大的可能性。     

光学成像技术在中医针刺研究中的应用进展

以针刺和拔罐疗法为代表的中医理疗被用于治疗肌肉骨骼疾病、缓解疼痛症状已有数千年的历史。中医理疗以疗效显著、安全性高的优势在全球流行。然而,传统的中医理论对于针刺疗法治疗机制的解释缺乏有效的科学证据,而且大多数针刺疗法的疗效缺乏有效的定量评估,无法保证其治疗效果及安全性。凭借高分辨率、高对比度、高安全性等特点,光学成像技术在针刺疗法的机制研究与疗效评估方面展现出了巨大潜力。目前用于研究针刺疗法的光学成像技术主要有激光多普勒血流灌注成像、激光散斑成像、近红外光谱成像和光声成像等,它们分别在针刺的血流动力学效应、大脑响应、治疗机制与疗效评估等方面取得了一定进展,但目前鲜见系统总结上述光学成像技术应用于针刺疗法研究的报道。鉴于此,本文系统介绍了这几类光学成像技术的特点以及它们在针刺疗法研究中的应用情况,并展望了其临床研究前景。     

金纳米棒的制备及其在光声成像中的应用

该文制备了巯基聚乙二醇（PEG）修饰的金纳米棒,该纳米材料在近红外区具有良好的光吸收特性,具备作为优良光声造影剂的潜质。该文通过透射电子显微镜（TEM）、紫外 可见（UV VIS）吸收光谱等测量手段对金纳米棒进行了形貌、结构、基本光学性能及光声成像效果等表征。实验结果表明,随着材料浓度的增加,体外光声信号的响应近似呈线性增长;经由PEG修饰,金纳米棒的生物相容性得到提高;PEG修饰后的金纳米棒对小鼠大脑皮层血管的成像效果得到提升。结果表明,PEG修饰的金纳米棒材料,在光声成像造影领域具有巨大的应用前景。     

基于波长编码的扫频光学相干内窥成像方法

提出了一种基于波长编码的扫频光学相干层析(SS-OCT)内窥成像方法,详细分析了该方法的工作原理,从理论分析上证明了其可行性.从系统时间脉冲响应和传递函数推导出系统干涉信号的数学表达式;模拟了简单样品的干涉信号,并给出Morlet小波分析的解码结果;讨论了系统的一些关键性能参数,如横向成像点数、成像分辨率、成像范围、成像速度等,指出系统横向分辨率和纵向分辨率相互制约,提高扫频光源的扫频范围是优化系统分辨率的有效方法.     

发光二极管光源疗法在生物医学中的应用

综述了国内外以发光二极管为光源的光疗法在生物医学中的应用研究,主要从动物体试验,动物细胞实验和医学临床进行了分析,对医学临床进行了重点的分析研究。并从安全性、经济性、使用性等多方面比较分析了发光二极管光源疗法与其它光源疗法的优缺点。发光二极管光源疗法将在生物医学领域有广阔的应用,在产品商业化上也会有较大的发展。     

Gold Nanoshell Nanomicelles for Potential Magnetic Resonance Imaging,Light‐Triggered Drug Release,and Photothermal Therapy

A novel multifunctional drug‐delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe₃O₄ magnetic nanoparticles, and gold nanoshells (CDF‐Au‐shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic‐targeted drug delivery, light‐triggered drug release, and photothermal therapy. The nanomicelles show improved drug‐encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T₂‐weighted MR imaging is observed for the CDF‐Au‐shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near‐infrared (NIR) region, thus exhibiting an NIR (808 nm)‐induced temperature elevation and an NIR light‐triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF‐Au‐shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF‐Au‐shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic‐field‐guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.     

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。     

Effective Eradication of Tumors by Enhancing Photoacoustic-Imaging-Guided Combined Photothermal Therapy and Ultrasonic Therapy

Exploiting a comprehensive strategy that processes diagnosis and therapeutic functions is desired for eradicating tumors. In this study, two versatile nanoparticles are introduced: one is polyethylene glycol- and polyethyleneimine-modified gold nanorods (mPEG–PEI–AuNRs), and the other is formed by electrostatic interactions between mPEG–PEI and calcium carbonate nanoparticles (mPEG–PEI/CaNPs). These two nanoparticles possess following favorable properties: 1) mPEG–PEI–AuNRs and mPEG–PEI/CaNPs show not only high cell uptake in acidic tumoral pH, but also efficient accumulation in tumors with prolonged circulation. 2) mPEG–PEI/CaNPs can generate carbon dioxide (CO₂) bubbles in acidic tumoral environment and the photoacoustic (PA) signals from mPEG–PEI–AuNRs can be enhanced with the generation of CO₂ bubbles. 3) The tumors can be eradicated by combining photothermal therapy (PTT) with ultrasonic therapy (UST) under the near-infrared (NIR) laser and ultrasonic irradiation with the presence of mPEG–PEI–AuNRs and CO₂ bubbles from mPEG–PEI/CaNPs. The detailed evaluation of cellular uptake, photothermal property of mPEG–PEI–AuNRs, CO₂ bubbles’ generation from mPEG–PEI/CaNPs, imaging, and combined PTT and UST are carried out in vitro or in vivo. This work has great potential usage for diagnosis and treatment in the future.     

Multifunctional Carbon–Silica Nanocapsules with Gold Core for Synergistic Photothermal and Chemo‐Cancer Therapy under the Guidance of Bimodal Imaging

Carbon‐based nanomaterials have been developed for photothermal cancer therapy, but it is still a great challenge to fabricate their multifunctional counterparts with facile methods, good biocompatibility and dispersity, and high efficiency for cancer theranostics. In this work, an alternative multifunctional nanoplatform is developed based on carbon–silica nanocapsules with gold nanoparticle in the cavity (Au@CSN) for cancer theranostics. The encapsulated chemodrug doxorubicin can be released from the Au@CSN with mesoporous and hollow structure in a near‐infrared light and pH stimuli‐responsive manner, facilitating spatiotemporal therapy to decrease off‐target toxicity. The nanocapsules with efficient photothermal conversion and excellent biocompatibility achieve a synergistic effect of photothermal and chemotherapy. Furthermore, the nanocapsules can act as a multimodal imaging agent of computed tomography and photoacoustic tomography imaging for guiding the therapy. This new design platform can provide a promising strategy for precise cancer theranostics.     

光学相干层析成像技术确定组织光学特性

光学相干层析成像(OCT)是近年来发展较快的一种新型成像技术,能对生物组织内部的微观结构进行高分辨率的横断面层析成像,具有快速、非侵入及高分辨率等特点,在体生物组织微观结构分析和疾病诊断等方面具有重要的应用价值.综述了采用光学相干层析成像技术确定生物组织光学特性的研究.     

Precise Starving Therapy via Physiologically Dependent Photothermal Conversion Promoted Mitochondrial Calcification Based on Multi-Functional Gold Nanoparticles for Effective Tumor Treatment

Starving therapy based on tumor calcification has been considered as a promising strategy with high biosafety for tumor treatment. However, the limited calcium (Ca²⁺) concentration in/around tumor tissue as well as the slow and uncontrollable process of the physiological calcification are all challenges for its application. Herein, a sialic acid (SA, Ca²⁺ chelator), folic acid (FA, tumor targeting agent) and triphenylphosphine (TPP, mitochondrial targeting agent) co-modified gold nanoparticles (SFT-Au) are fabricated to take advantage of the abundant Ca²⁺ in mitochondria as well as the Ca²⁺ collection and Ca²⁺ dependent photothermal property of SFT-Au to achieve a precise and promoted calcification of tumor mitochondria for effective starving therapy. During therapy, the SFT-Au will first accumulate in tumor mitochondria through stepwise targeting processes medicated by FA and TPP. After that, the SA further binds with the over-expressed Ca²⁺ in tumor mitochondria to induce the aggregation of SFT-Au, which not only gathers Ca²⁺ to initiate the calcification of mitochondria, but in situ generates photothermal agent to perform photothermal conversion under 808 nm irradiation to promote the calcification, resulting in effective prohibition of the energy metabolism in tumor cells for starving therapy and continuously photothermal damage of tumor cells to enhance the therapeutic efficiency.     

Biocompatible D–A Semiconducting Polymer Nanoparticle with Light‐Harvesting Unit for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy

The development of nanotheranostic agents that integrate diagnosis and therapy for effective personalized precision medicine has obtained tremendous attention in the past few decades. In this report, biocompatible electron donor–acceptor conjugated semiconducting polymer nanoparticles (PPor‐PEG NPs) with light‐harvesting unit is prepared and developed for highly effective photoacoustic imaging guided photothermal therapy. To the best of our knowledge, it is the first time that the concept of light‐harvesting unit is exploited for enhancing the photoacoustic signal and photothermal energy conversion in polymer‐based theranostic agent. Combined with additional merits including donor–acceptor pair to favor electron transfer and fluorescence quenching effect after NP formation, the photothermal conversion efficiency of the PPor‐PEG NPs is determined to be 62.3%, which is the highest value among reported polymer NPs. Moreover, the as‐prepared PPor‐PEG NP not only exhibits a remarkable cell‐killing ability but also achieves 100% tumor elimination, demonstrating its excellent photothermal therapeutic efficacy. Finally, the as‐prepared water‐dispersible PPor‐PEG NPs show good biocompatibility and biosafety, making them a promising candidate for future clinical applications in cancer theranostics.     

Intracellular Nanoparticle Formation and Hydroxychloroquine Release for Autophagy-Inhibited Mild-Temperature Photothermal Therapy for Tumors

Mild-temperature photothermal therapy (PTT) of tumors has been intensively explored and adopted in preclinical/clinical trials in recent years. Nevertheless, tumor thermoresistance significantly compromises the therapeutic efficacy of mild-temperature PTT, and therefore, the extra addition of anti-thermoresistance agent is needed. Herein, by rational design of a peptide-hydroxychloroquine (HCQ) conjugate Cypate-Phe-Phe-Lys(SA-HCQ)-Tyr(H₂PO₃)-OH (Cyp-HCQ-Yp), a “smart” strategy of enzyme-triggered simultaneously intracellular photothermal nanoparticle formation and HCQ release is proposed for autophagy-inhibited mild-temperature PTT of tumor. In vitro results show that, under sequential catalysis of enzymes alkaline phosphatase and carboxylesterase, Cyp-HCQ-Yp is converted to Cypate-Phe-Phe-Lys(SA)-Tyr-OH (Cyp-Y) which self-assembles into its nanoparticle Cyp-NP and HCQ is released from Cyp-HCQ-Yp. By comparing with two control agents, it is validated that the exceptional therapeutic effect of Cyp-HCQ-Yp on tumor in vivo is achieved by its dual-enzyme-controlled intracellular nanoparticle formation and autophagy inhibition in tumors.     

Gold Nanorods Electrostatically Binding Nucleic Acid Probe for In Vivo MicroRNA Amplified Detection and Photoacoustic Imaging‐Guided Photothermal Therapy

Developing a comprehensive platform which has both diagnosis and therapeutic strategies is necessary for efficient tumor treatment. In this work, a F uel I mproved micro R NA E xplorer (FIRE) probe with signal amplification capability is designed for sensitive detection of microRNA‐21 (miR‐21), which is upregulated in most tumor cells. Besides, FIRE could be loaded by polyethylenimine (PEI)‐modified gold nanorods (AuNR‐PEI) via facile electrostatic interaction, which could avoid the complicated processes commonly used to covalently conjugate nucleic acid probes onto AuNRs. The as‐fabricated AuNR‐PEI/FIRE system could efficiently distinguish tumor cells from non‐tumor cells. The fluorescence signals in MCF‐7 breast carcinoma and HeLa cervical carcinoma cells treated with AuNR‐PEI/FIRE are enhanced 7‐ and 4.5‐fold, respectively, compared with non‐amplification system. AuNR‐PEI/FIRE improves tumor detection ability in vivo and exhibits excellent tumor inhibition efficacy under the fluorescence imaging and photoacoustic imaging guided photothermal therapy. This is the first time to utilize the combined application of amplified nucleic acid detection and photothermal effect derived from gold nanorods together with PA imaging in a facile manner to provide a promising theranostic strategy for accurate diagnosis and tumor therapy.