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.

Vascular-targeted photodynamic therapy (V-PDT) is an effective treatment for port wine stains (PWS). However, repeated treatment is usually needed to achieve optimal treatment outcomes, possibly due to the limited treatment light penetration depth in the PWS lesion. The optical clearing technique can increase light penetration in depth by reducing light scattering. This study aimed to investigate the V-PDT in combination with an optical clearing agent (OCA) for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model. Vascular responses were closely monitored with laser speckle contrast imaging (LSCI), optical coherence tomography angiography, and stereo microscope before, during, and after the treatment. We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature. The combination of OCA and V-PDT resulted in significant vascular damage, including vasoconstriction and the reduction of blood flow. Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases, including PWS.

Photodynamic therapy (PDT) has limited effects in treating metastatic breast cancer. Immune checkpoints can deplete the function of immune cells; however, the expression of immune checkpoints after PDT is unclear. This study investigates whether the limited efficacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the efficacy. A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives (HpD-PDT). The anti-tumor effect of HpD-PDT was observed, as well as CD4+T, CD8+T and calreticulin (CRT) by immunohistochemistry and immunofluorescence. Immune checkpoints on T cells were analyzed by flow cytometry after HpD-PDT. When combining PDT with immune checkpoint inhibitors, the antitumor effect and immune effect were assessed. For HpD-PDT at 100mW/cm² and 40, 60 and 80J/cm², primary tumors were suppressed and CD4+T, CD8+T and CRT were elevated; however, distant tumors couldn’t be inhibited and survival could not be prolonged. Immune checkpoints on T cells, especially PD1 and LAG-3 after HpD-PDT, were upregulated, which may explain the reason for the limited HpD-PDT effect. After PDT combined with anti-PD1 antibody, but not with anti-LAG-3 antibody, both the primary and distant tumors were significantly inhibited and the survival time was prolonged, additionally, CD4+T, CD8+T, IFN-γ+CD4+T and TNF-α+CD4+T cells were significantly increased compared with HpD-PDT. HpD-PDT could not combat metastatic breast cancer. PD1 and LAG-3 were upregulated after HpD-PDT. Anti-PD1 antibody, but not anti-LAG-3 antibody, could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

光动力疗法（PDT）是一种通过光动力反应选择性地治疗恶性肿瘤及癌前病变等疾病的新型疗法，具有广阔的临床应用前景。光敏剂作为PDT的关键要素之一，其在体浓度分布直接影响PDT疗效，实现光敏剂剂量在体定量检测是开展个性化PDT精准治疗的前提。介绍了光敏剂浓度在体定量检测的影响因素；总结了目前常用的光敏剂荧光光谱定量校准方法及荧光定量检测技术；最后讨论了光敏剂定量检测技术在PDT临床转化应用中所面临的挑战和发展方向。

Photodynamic therapy (PDT) not only destroys tumor cells directly but also induced anti-tumor immune response through damage-associated molecular patterns (DAMPs). It is reported that anti-tumor response was associated with light dose and photosensitizer used in PDT. In this study, 4T1 tumor cells were implanted on both the right and left flanks of mice. Only the right tumor was treated by HpD-PDT, while the left tumor was not irradiated. The anti-tumor immune response induced by HpD-PDT was investigated. The expression of DAMPs and costimulatory molecules induced by HpD-PDT were tested by immunofluorescence and flow cytometry in vivo. Different light doses of PDT were designed to treat 4T1 cells. The killing effect was assessed by CCK-8 kit and apoptosis kit. The expression of DAMPs on 4T1 cells after HpDPDT were evaluated by flow cytometry, western blot and ATP kit. This study showed that CD4tT, CD8tT and the production of IFN-γ were increased significantly on day 10 in righttumor after PDT treatment compared with control group. HpD-PDT enhanced the expression of calreticulin (CRT) on tumor tissue. Importantly, co-stimulatory molecular OX-40 and 4-1BB were elevated on CD8tT cells. In vitro, immunogenic death of 4T1 cells was induced after PDT. Besides, the expression of DAMPs increased with the increasing of energy density. This study indicates that anti-tumor immune effect was induced by HpD-PDT. The knowledge of the involvement of CRT, ATP and co-stimulatory molecules uncovers important mechanistic insight into the anti-tumor immunogenicity. It was the first time that co-stimulatory molecules were investigated and found to elevate after PDT.

鲜红斑痣(port wine stains, PWS)是最常见的先天性皮肤微血管病变之一，PWS的病因是皮肤真皮层由浅至深的毛细血管畸形扩张。通常表现为面颈部粉色、红色和紫色斑片，随着年龄的增加，其逐渐加深和增厚，严重影响患者的生活质量。血管靶向光动力疗法 (vascular targeted photodynamic therapy, V-PDT) 可以选择性破坏病变血管，是目前国内治疗PWS的首选方法。V-PDT疗效与PWS病灶结构密切相关。PWS的病灶结构可通过活检或者无创光学诊断设备获取，主要包括表皮层黑色素含量、皮肤厚度及血管管径、深度和形态等。总结了目前常用的无创在体光学成像技术在PWS诊疗中的应用现状及PWS病灶结构特点对V-PDT疗效的影响，旨在为V-PDT精准及个性化治疗PWS提供参考。

Photobiomodulation (PBM) promoting wound healing has been demonstrated by many studies. Currently, 630 nm and 810 nm light-emitting diodes (LEDs), as light sources, are frequently used in the treatment of diabetic foot ulcers (DFUs) in clinics. However, the dose–effect relationship of LED-mediated PBM is not fully understood. Furthermore, among the 630 nm and 810 nm LEDs, which one gets a better effect on accelerating the wound healing of diabetic ulcers is not clear. The aim of this study is to evaluate and compare the effects of 630 nm and 810 nm LED-mediated PBM in wound healing both in vitro and in vivo. Our results showed that both 630 nm and 810 nm LED irradiation significantly promoted the proliferation of mouse fibroblast cells (L929) at different light irradiances (1, 5, and 10mW/cm2. The cell proliferation rate increased with the extension of irradiation time (100, 200, and 500 s), but it decreased when the irradiation time was over 500 s. Both 630 nm and 810 nm LED irradiation (5mW/cm2 significantly improved the migration capability of L929 cells. No difference between 630 nm and 810 nm LED-mediated PBM in promoting cell proliferation and migration was detected. In vivo results presented that both 630 nm and 810 nm LED irradiation promoted the wound healing and the expression of the vascular endothelial growth factor (VEGF) and transforming growth factor (TGF) in the wounded skin of type 2 diabetic mice. Overall, these results suggested that LED-mediated PBM promotes wound healing of diabetic mice through promoting fibroblast cell proliferation, migration, and the expression of growth factors in the wounded skin. LEDs (630 nm and 810 nm) have a similar outcome in promoting wound healing of type 2 diabetic mice.

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.

血管靶向光动力疗法(Vascular targeted photodynamic therapy, V-PDT)已成为临床治疗鲜红斑痣和老年黄斑变性等血管性疾病的重要方法。V-PDT通过主动或被动血管靶向的作用机制诱发系列生物响应以封闭病变血管。本文评述了V-PDT的作用机制和血管生物学响应, 重点讨论了用于评估V-PDT中血管损伤的光谱与成像技术, 并分析了这些技术的优点和局限性。最后展望了用于评估V-PDT血管损伤的光学技术发展及其应用前景。

血管中的血氧饱和度（Oxygen saturation，StO2）作为影响血管靶向光动力疗法（Vascular targeted photodynamic therapy，V-PDT）疗效的关键要素之一，实验测量了活体裸鼠背皮窗模型中血管的漫反射光谱（450-800 nm），并通过拟合漫反射光谱数据定量获得了血管中的StO2。同时，研究了高氧、低氧和常氧等三种不同氧条件下V-PDT中血管的StO2和血管管径的变化情况。结果表明，高氧和常氧条件下的平均StO2和血管收缩较为显著，但低氧组的平均StO2和血管收缩不明显。在相同氧条件和不同光照功率密度条件下，V-PDT前后靶向血管的平均StO2与血管管径的变化之间没有显著相关性，但V-PDT前后平均StO2的变化量与光照功率密度之间呈正相关。