光敏剂特性影响光动力治疗鲜红斑痣的数学仿真研究

目的：通过建立光动力治疗鲜红斑痣中激光、光敏剂、氧的分布及其相互作用关系的数学模型,对表皮、真皮、血管中单线态氧的产生过程进行仿真,了解光敏剂的药代动力学和扩散特性对单线态氧产生的影响,进而了解光敏剂特性在光动力治疗鲜红斑痣中的作用和意义。方法：用’Monte Carlo方法描述光在组织中的分布;用药代动力学描述光敏剂在血管中的变化规律;用Fick定律描述光敏剂和氧在组织中的扩散和分布;用与氧含量有关的二级动力学描述光敏剂的漂白;用Lambert—Beer定律和单线态氧的量子产率来计算各层组织中单线态氧的产生。结果：光敏剂药代动力学的变化,使注射光敏剂后开始照光的时间对各层组织中单线态氧产量有明显的影响。光敏剂扩散特性的改变,对真皮和表皮中单线态氧的产生有较大影响,对血管中单线态氧的产生没有影响。结论：光敏剂的特性对光动力治疗鲜红斑痣有明显的影响,数学仿真能较全面地反应这种作用的特点和意义。     

光动力疗法过程中的光漂白特性

基于光动力过程中的光分布规律,研究了半无限大组织中组织光学特性和光分布对光漂白作用效果的影响.研究发现光漂白效果与组织的散射系数和吸收系数成反比;光漂白的有效作用深度是4.5 mm,最大作用深度是33 mm.研究所得结果不仅表明通过光分布研究光漂白的特性是一种有效的方法,而且对临床上设计合理的治疗法案具有重要的参考作用...     

抗菌光敏剂的分类及研究进展

目前控制细菌和病毒感染性疾病的方法很多,但由于微生物菌株种类越来越多,且耐药微生物菌株不断涌现,已有的治疗手段无法取得良好疗效,因此探索新的抗微生物治疗方法迫在眉睫。光动力抗菌化学疗法是基于光动力疗法的原理,利用光敏剂在异常组织选择性聚集,在分子氧的参与下,由特定波长的光激发产生活性氧,引发一系列的光化学反应,对微生物进行选择性杀伤的一种新方法。光动力抗菌化学疗法对细菌、真菌和病毒引起的感染,特别是耐药菌感染均显示很好的疗效。本文将对光动力抗菌化学疗法中常使用的光敏剂进行分类,并对其研究进展进行综述。     

荧光探针在光动力疗法亚细胞损伤位点研究中的应用

目的：应用荧光探针在光动力疗法研究中检测亚细胞损伤位点。方法：传代培养鼠肺毛细血管内皮细胞,将血卟啉单甲醚(HMME)与内皮细胞共同孵育24小时后,加入线粒体探针Bhodamine-123、内质网探针DioC6(3)和溶酶体探针Lucifer yellow分别对细胞器染色。首先采用激光共聚焦显微镜对光敏剂进行亚细胞定位。应用荧光显微镜汞灯照射激发光敏剂的光动力效应,加入ROS探针H2DCF-DA检测产生的单线态氧。分别在激发前后采集Pdloclamine-123、Lucifer yellow和DioC6(3)的荧光图像。结果：线粒体探针Phodamine-123的荧光图像在光动力损伤前后差异显著,原有形态特点发生明显改变;Phodamine-123在光动力损伤后再分布于细胞核区。结论：血卟啉单甲醚介导的光动力效应导致亚细胞水平多位点损伤,线粒体和核膜可能是PDT敏感位点;荧光探针标记检测光动力损伤亚细胞位点方法简便可靠。     

聚合物纳米粒在肿瘤光动力治疗中的研究进展

光动力治疗创伤小,在恶性肿瘤治疗方面的应用已经得到了临床认可。治疗过程中需要给予光敏剂,在光照下产生分子氧对肿瘤细胞产生杀伤作用。但是,大多数光敏剂缺乏对肿瘤细胞的特异性,其在肿瘤中的富集主要与细胞高代谢有关,并且在水相媒介中溶解度比较差。纳米技术应用于光动力治疗提供了一种有效地体内运输光敏剂的方式。目前,聚合物纳米粒与光动力药物传递的研究越来越多,光敏剂通过纳米粒的运输为弥补光动力治疗的不足提供了可能,这是因为纳米载体可以将治疗浓度的光敏剂运送到肿瘤细胞而不造成非靶向组织的副损伤。本文将介绍对肿瘤光动力治疗中具有特异性的聚合物纳米粒的种类及在临床中的应用情况,为肿瘤靶向治疗提供新思路。     

低氧环境对细胞培养基内氧浓度的影响

目的:测定不同氧环境下细胞培养基内的实际氧浓度,并探讨在细胞培养过程中,影响培养基内氧含量的因素。方法:利用光纤氧传感探头,对不同氧环境下、不同细胞培养容器中,以及常氧或低氧环境下换液前后RPMI1640培养基内的氧含量进行测定。结果:培养基中的氧含量可以随着外界氧环境的变化而改变;低氧环境下24孔板和35 mm皿中的氧含量要比25 cm2培养瓶稳定;常氧环境下换液使得培养基内的氧含量明显升高,而在低氧环境下换液则对培养基内的氧含量无明显影响。结论:在不同氧浓度下的细胞培养模型研究中,严格控制外界环境中的氧浓度,选用合适的细胞培养容器,并且在换液过程中尽量避免或减少培养基与常氧环境的接触,是维持培养基内氧含量稳定的重要因素。     

空气氧的环境生态学效应

空气氧作为自然界生物圈中生物群落生存和发展的重要物质基础 ,其含量直接关系着人类的健康 ;同时 ,做为生态系统的核心组分之一 ,空气氧可通过一系列环境生态效应对微小生态进行调节 ,由此所产生的对人群的间接生物学效应也日益受到关注 ,特别是与提高环境质量的关系不容忽视。本文简述空气氧的有关环境生态学效应。1　空气氧含量与空气物理特性Ｏ2 作为空气化学组成的重要成分 ,可影响空气中的太阳辐射、电离、离子化等物理性状及其生物学效应[1,2 ] 。1 1　空气氧与空气离子化　空气分子和原子在自然或人为条件下 ,失去电子成为空气正离…     

光声成像在光动力疗法研究中的应用

组织氧合作用和光敏剂应用在疾病诊治中都有着重要的作用,因此其实时在体无损检测很有意义。光动力疗法涉及光敏剂、光和氧分子三大要素,其疗效受组织氧合作用影响。本文对光声成像(PAI)、光声寿命成像(PALI)和多光谱光声层析成像(MSOT)等光声成像技术在光动力疗法的研究和应用中的使用现状进行了综述。对相关设备系统在检测光敏剂、组织氧分压和微血管损伤等方面的应用原理和技术分别进行了介绍,并总结了这些技术的应用前景。     

蒙特卡罗模拟多束光辐照下生物组织中的光吸收分布

用蒙特卡罗方法模拟了均匀分布光和高斯分布光在生物组织内的传播。通过比较单束以及多束均匀分布光和高斯分布光照射下组织内的光子能量分布规律,分析了不同光源和光斑大小对光吸收分布的影响。结果表明:与均匀光束比较,高斯光束辐照时,激光能量较为集中,但侧向传播范围较窄。在总功率相同的情况下,使用单束大功率宽光源与多束功率较小的小光斑光源均能明显地增大光的侧向传播距离,但使用多束功率较小的小光斑光辐照时生物组织中的最大光吸收率增大。多束组合光源光束间距对光吸收分布影响很大。     

光动力学疗法对真菌生物膜的作用研究进展

生物膜是一种附着于活组织或无活力组织的表面、由菌体产生的细胞外多聚基质包裹的有结构的菌细胞群体。近年来,有研究表明随着真菌耐药性的增加,65%的感染与生物膜的形成有关,光动力疗法作为一种新型非侵入性疗法,具有精确靶向特性,已广泛用于实体肿瘤的治疗,目前人们发现其对真菌生物膜的治疗方面有良好的前景。该文就光动力疗法对真菌生物膜的作用进行综述,旨在让大家对光动力抗真菌治疗有一个全面深入的了解。     

Nonlinear photodynamic therapy: method of pulsed oxygen depletion.

The photodynamic therapy technique involving pulsed oxygen depletion (POD) in tissue by long high-energy pulses of light was studied theoretically. The possibility of creating a uniform distribution of a therapeutic dose throughout a tumor using both surface and interstitial irradiation is shown. Possible thickness of the treated tissue layer is estimated. The comparison with other methods of nonlinear photodynamic therapy is made.     

Dosimetry in photodynamic therapy: oxygen and the critical importance of capillary density.

Recently published results of tumor response to various photoradiation protocols in photodynamic therapy appear to contradict accepted definitions of photodynamic dose. In this report, the failure of standard dosimetry models to predict therapeutic outcome is interpreted on the basis of PDT-induced oxygen consumption in tumors with relatively low capillary densities. Calculated estimates of oxygen consumption in photodynamic therapy are combined with the Krogh cylinder model of oxygen diffusion. It is shown that, for tissue volumes in which the intercapillary spacing is less than a specific critical distance, oxygen may be considered constant and unaffected by the therapy. Under these conditions, the 1O2 delivered to a given volume of tissue is spatially uniform and proportional to the number of photons absorbed by the sensitizer. When the intercapillary spacing exceeds the critical distance, the dose of 1O2 varies with radial distance from the capillary wall. In this situation, dose may no longer be considered simply in terms of the product of the photon fluence and the sensitizer absorption coefficient. Since fractionation will increase the 1O2 dose only to cells relatively remote from the capillary wall, the analysis further suggests that fractionating the radiation dose should result in an improved therapeutic ratio for photodynamic therapy.     

Tumor PO(2) changes during photodynamic therapy depend upon photosensitizer type and time after injection

In this study, the vascular and tissue oxygen changes induced by photodynamic therapy in the RIF-1 tumor were examined, using electron paramagnetic resonance (EPR) oximetry. Two photosensitizers, including verteporfin (BPD-MA in a lipid-based formulation) and aminolevulinic acid-induced protoporphyrin IX (ALA-PPIX), were investigated with optical irradiation, sufficient to induce sub-curative damage in the tumor tissue, and the transient changes in PO(2) and vascular perfusion were examined. A large increase in tissue oxygenation (from 3 up to 9.5 mmHg) was observed when treated with ALA-PPIX based photodynamic therapy, which lasted during the treatment and a small residual increase that returned back to baseline levels by 48 h after treatment. With verteporfin-based photodynamic therapy, one group of animals was irradiated 15 min after injection and exhibited a small decrease in oxygenation relative to pre-irradiation levels. The second group was irradiated at 3 h after injection and exhibited a large increase in the average PO(2), (from 3 to 15 mmHg) by the end of the treatment. These observations indicate that photodynamic therapy significantly increases tissue PO(2) under certain treatment conditions, with the potential cause being either increased local blood flow or decreased local oxygen metabolic consumption due to cellular damage.     

Cycloimide bacteriochlorin p derivatives: photodynamic properties and cellular and tissue distribution

Reactive oxygen species generated by photosensitizers are efficacious remedy for tumor eradication. Eleven cycloimide derivatives of bacteriochlorin p (CIBCs) with different N-substituents at the fused imide ring and various substituents replacing the 3-acetyl group were evaluated as photosensitizers with special emphasis on structure-activity relationships. The studied CIBCs absorb light within a tissue transparency window (780-830 nm) and possess high photostability at prolonged light irradiation. The most active derivatives are 300-fold more phototoxic toward HeLa and A549 cells than the clinically used photosensitizer Photogem due to the substituents that improve intracellular accumulation (distribution ratio of 8-13) and provide efficient photoinduced singlet oxygen generation (quantum yields of 0.54-0.57). The substituents predefine selective CIBC targeting to lipid droplets, Golgi apparatus, and lysosomes or provide mixed lipid droplets and Golgi apparatus localization in cancer cells. Lipid droplets and Golgi apparatus are critically sensitive to photoinduced damage. The average lethal dose of CIBC-generated singlet oxygen per volume unit of cell was estimated to be 0.22 mM. Confocal fluorescence analysis of tissue sections of tumor-bearing mice revealed the features of tissue distribution of selected CIBCs and, in particular, their ability to accumulate in tumor nodules and surrounding connective tissues. Considering the short-range action of singlet oxygen, these properties of CIBCs are prerequisite to efficient antitumor photodynamic therapy.     

藻红蛋白光敏剂研究进展

光动力学治疗法作为一种新的肿瘤治疗方法,近年来发展十分迅速。从红藻中提取的藻红蛋白可以作为光动力学治疗法的一种新的光敏剂。本概述了我国红藻藻红蛋白资源概况、光疗法和光敏剂作用机理及其研究发展历史与现状,重点阐述了藻红蛋白光敏剂的应用现状、前景和发展趋势,并认为藻红蛋白是光动力学治疗法中一种非常有前景的光敏剂。藻红蛋白在490nm有吸收光谱,而发射光谱位于560nm;藻红蛋白能特异性地聚集在肿瘤细胞周围,吸收周围环境光能并传递给氧分子,使氧分子转化为具有强氧化性的多线态氧,从而可以大量杀死肿瘤细胞。     

带有功能性多肽的光敏剂及其应用

光动力治疗( photodynamic therapy,PDT )是光敏剂在特定波长光源的激发下、在氧分子存在下产生细胞毒性物质的一种治疗方法,主要用于抗肿瘤治疗．目前临床应用的光敏剂对肿瘤细胞的靶向性比较有限,近来的一个热门研究方向是靶向性光敏剂．结合作者多年来在该方向的工作,综合近年来光敏剂研究的发展,比较全面地阐述了带有功能性多肽的靶向性光敏剂及其在光动力治疗中的应用．阐述多肽作为靶向基团的优势,总结了包括透膜多肽、血管靶向多肽、细胞受体靶向多肽等功能多肽与光敏剂偶合物的生物效应,说明了多肽能够实现光敏剂的靶向作用．     

The Involvement of Autophagy in the Response of Neurons and Glial Cells to Photodynamic Treatment

Photodynamic therapy is used for selective destruction of pathological tissue in oncology; this method is also employed for ablation of brain tumors. Cell death upon photodynamic treatment results from oxidative stress that develops in photosensitized cells upon exposure to light in the presence of oxygen. We studied the development of autophagy during photo-induced oxidative stress in a crayfish stretch receptor that consists of two sensory neurons in a glial envelope by measuring the number and distribution of lysosomes using a LysoTracker Red fluorescent probe. Photodynamic treatment with radachlorin (500 nM) for 15 min decreased the number of lysosomes, probably due to their photodestruction. However, 1 h after the photodynamic treatment with radachlorin (250 nM) the LysoTracker Red fluorescence increased with larger granules occurring, which may be indicative of autophagic processes in the cell. Photodynamic treatment is capable of inducing necrosis of neurons and glial cells and glial apoptosis in a crayfish stretch receptor. Modulation of autophagy by application of specific inhibitors and activators of AMPK (AICAR, dorsomorphin) and mTOR (rapamycin, KU0063794) revealed that autophagy could protect glia against photo-induced cell death.     

Reactive oxygen-dependent production of novel photochemotherapeutic agents.

The reactive nature of species derived from oxygen, such as singlet oxygen and hydrogen peroxide, has been exploited in the clinical setting for targeting bacteria, viruses, and tumor cells by photodynamic excitation of a variety of chromophores. This modality, termed photodynamic therapy (PDT), is currently being used to treat some forms of cancer. However, the applicability of conventional PDT is limited due to the absolute dependence on simultaneous exposure of the target to the photoactive compound and light. In 1990, we demonstrated that the need for simultaneous exposure of the biological target to light and photosensitizer could be circumvented by prior exposure (activation) of the sensitizer molecule to light and its subsequent use as any other anti-cancer or anti-viral drug. By dint of the nature of the protocol, this process was termed preactivation. Since then, the generation of biologically active molecules in vitro by preactivation has been validated using a variety of chromophores, such as merocyanine 540, Photofrin II, and naphthalimide. Here we briefly review the role of reactive oxygen species in the photodynamic effect, and provide an explanation for the mechanism of preactivation. We propose that photo-oxidation not only provides a novel means for the generation of biologically active molecules, but could also explain, at least in part the mechanism of conventional PDT. It is likely that the light-dependent breakdown of the chromophore to generate novel active compounds, in addition to reactive oxygen species, also contributes to the photodynamic damage observed on simultaneous exposure of the chromophore and target tissue to light during PDT.-Pervaiz, S. Reactive oxygen-dependent production of novel photochemotherapeutic agents.