Photodynamic therapy (PDT) has been increasingly used in the clinical treatment of neoplastic, inflammatory and infectious skin diseases. However, the generation of reactive oxygen species (ROS) may induce undesired side effects in normal tissue surrounding the treatment lesion, which is a big challenge for the clinical application of PDT. To date, (–)-Epigallocatechin gallate (EGCG) has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage. This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether (Hemoporfin)-mediated PDT. The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized ¹O₂ generation are determined to be 6.8×108 M^?1S^?1 and 1.5×108 M^?1S^?1, respectively. The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel, suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG. This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and ¹O₂, and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

自2001年被发明以来，超导纳米线单光子探测器（SNSPD）迅速成长为近红外波段的明星光子探测器，其在近红外波段如1550 nm处系统探测效率超过95%，暗计数率低于1 cps（counts per second），时间抖动优于10 ps，探测速率高于1 GHz，并广泛应用在量子信息领域。近年来，研究人员开始将SNSPD引入到生物领域，以替代在近红外波段具有低信噪比、多后脉冲的半导体单光子探测器。本文将介绍SNSPD的探测原理和性能指标，并系统地阐述SNSPD在生物领域中的应用现状和发展前景。

Singlet oxygen (¹O₂) is the main cytotoxic substance in Type II photodynamic therapy (PDT). The luminescence of ¹O₂ at 1270nm is extremely weak with a low quantum yield, making the direct detection of ¹O₂ at 1270nm very challenging. In this study, a set of highly sensitive optical fiber detection system is built up to detect the luminescence of photosensitized ¹O₂. We use this system to test the luminescence characteristics of ¹O₂ in pig skin tissue ex vivo and mouse auricle skin in vivo. The experimental results show that the designed system can quantitatively detect photosensitized ¹O₂ luminescence. The ¹O₂ luminescence signal at 1270nm is successfully detected in pig skin ex vivo. Compared with RB in an aqueous solution, the lifetime of ¹O₂ increases to 17.4±1.2μs in pig skin tissue ex vivo. Experiments on living mice suggest that an enhancement of ¹O₂ intensity with the increase of the TMPyP concentration. When the dose is 25mg/kg, the vasoconstriction can reach more than 80%. The results of this study hold the potential application for clinical PDT dose monitoring using an optical fiber detection system.Singlet oxygen (¹O₂) is the main cytotoxic substance in Type II photodynamic therapy (PDT). The luminescence of ¹O₂ at 1270nm is extremely weak with a low quantum yield, making the direct detection of ¹O₂ at 1270nm very challenging. In this study, a set of highly sensitive optical fiber detection system is built up to detect the luminescence of photosensitized ¹O₂. We use this system to test the luminescence characteristics of ¹O₂ in pig skin tissue ex vivo and mouse auricle skin in vivo. The experimental results show that the designed system can quantitatively detect photosensitized ¹O₂ luminescence. The ¹O₂ luminescence signal at 1270nm is successfully detected in pig skin ex vivo. Compared with RB in an aqueous solution, the lifetime of ¹O₂ increases to 17.4±1.2μs in pig skin tissue ex vivo. Experiments on living mice suggest that an enhancement of ¹O₂ intensity with the increase of the TMPyP concentration. When the dose is 25mg/kg, the vasoconstriction can reach more than 80%. The results of this study hold the potential application for clinical PDT dose monitoring using an optical fiber detection system.

Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy (APDT) is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms. Among the photosensitizers (PSs), compounds based on cationic porphyrins/metalloporphyrins are most successfully used to inactivate microorganisms. Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia. The aim of this work was to determine and test the most effective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms. It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria, including the methicillinresistant S. aureus strain. Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs. The effectiveness of these Zn–metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation. It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors: the presence in the porphyrin macrocycle of a positive charge (+4), a central metal atom (Zn2tT and hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen. The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins can find wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APDT.

为了实现光动力治疗过程中单线态氧的检测, 设计了一种水溶性良好的单线态氧纳米探针。首先利用再沉淀法将1,3二苯基异苯并呋喃(DPBF)封装于纳米颗粒中, 然后对纳米探针进行透射电镜、动态光散射粒径和吸收光谱表征, 表明纳米颗粒具有良好的分散性, 粒径约为200 nm, 在426 nm左右具有DPBF的特征吸收峰, 最后选择吲哚菁绿(ICG)作为光敏剂, 利用纳米探针的吸收峰变化检测单线态氧的产生。结果表明该纳米探针对单线态氧具有高灵敏度, 在光动力治疗过程中单线态氧的检测方面具有良好的应用价值。

以3-硝基邻苯二甲腈与3-巯基-1-丙磺酸钠为原料, 在醋酸盐存在下通过四环化合成了三种带四个3-磺基丙基磺酰基的水溶性酞菁。 利用紫外-可见吸收光谱, 荧光光谱等对其光谱性质进行了测量, 并计算了其荧光量子产率和单线态氧量子产率。 引入吸电子基团所合成的水溶性酞菁与ZnPc相比, 其荧光发射光谱的形状并未改变, 但其最大荧光发射波长均发生10 nm以上的红移。 三种水溶性酞菁中锌酞菁的荧光量子产率最高, 铜酞菁的荧光量子产率最低; 它们在水溶液中的荧光呈双指数衰减, 这可归结为激发态质子化或去质子化的结果。 单线态氧量子产率锌酞菁最大, 空心酞菁次之, 铜酞菁最小。 光谱分析结果表明, 合成的锌酞菁和空心酞菁具有高的单线态氧量子产率和高的光稳定性, 有望用作光动力治疗和光免疫治疗的光敏剂。

探讨光敏剂锌酞菁体外光动力疗法（ZnPc-PDT）抗肿瘤细胞的量效关系，为合理使用ZnPc提供参考。采用人脑胶质瘤细胞（U87 MG细胞）作为研究对象，用噻唑蓝(MTT)实验考察细胞存活率。采用单一变量的研究方法，分别考察了ZnPc浓度、激光功率密度、光照时间、体系氧含量和组织厚度等参量与U87 MG细胞存活率的关系。利用1,3-二苯基苯并呋喃(DPBF)和DCFH-DA活性氧探针分别检测了ZnPc-PDT过程中单线态氧的产量，并通过倒置显微镜观察经ZnPc-PDT治疗后的细胞形态和死亡细胞比例。结果表明，随着参量设置的变化，ZnPc-PDT对U87 MG细胞的杀伤力具有差异，通过调节参量，可达到较好的ZnPc-PDT治疗效果。

Pulsed and continuous-wave (CW) lasers have been widely used as the light sources for photodynamic therapy (PDT) treatment. Singlet oxygen (¹O₂) is known to be a major cytotoxic agent in type-II PDT and can be directly detected by its near-infrared luminescence at 1270 nm. As compared to CW laser excitation, the effects of pulse width and repetition rate of pulsed laser on the kinetics and production of ¹O₂ luminescence were quantitatively studied during photosensitization of Rose Bengal. Significant difference in kinetics of ¹O₂ luminescence was found under the excitation with various pulse widths of nanosecond, microsecond and CW irradiation with power of 20mW. The peak intensity and duration of ¹O₂ production varied with the pulse widths for pulsed laser excitation, while the ¹O₂ was generated continuously and its production reached a steady state with CW excitation. However, no significant difference (P > 0:05) in integral ¹O₂ production was observed. The results suggest that the PDT efficacy using pulsed laser may be identical to the CW laser with the same wavelength and the same average fluence rate below a threshold in solution.

构建由脂肪乳剂和墨水组成的皮肤组织模型, 定量研究皮肤组织模型的吸收系数μa和散射系数μs对光敏化单线态氧(singlet oxygen, 1O2)发光特性的影响。利用1O2发光检测系统测量含光敏剂四硫磺基酞菁氯化铝的皮肤组织模型分别在中心波长为1 230, 1 270和1 310 nm处的时间分辨发光光谱, 对扣除背景信号后的时间分辨1O2发光光谱进行积分和拟合, 获得1O2发光积分强度以及激发三重态寿命τT和1O2寿命τD。结果表明在皮肤组织模型中, 1O2发光积分强度随着μa和μs的增大而减小, μa对τT和τD没有影响。τT随着μs的增加而增加, τD随μs的增加先骤降而后缓慢上升。当μa>1.5 mm-1和μs>32 cm-1时, 1O2发光积分强度和τT、τD均趋于稳定, 其中τT和τD分别为3.4±0.6 μs和3.3±0.7 μs。