以光敏剂为基础的光动力疗法已被确定为许多肿瘤、皮肤性疾病、血管性疾病等适应证的安全治疗方式。在近些年的研究中，卟啉类光敏剂、二氢卟吩类光敏剂等均投入临床使用，酞菁类光敏剂、稠环醌类光敏剂等均已开展临床研究。但是，光动力疗法在临床转化中还面临着诸多问题，如有限的穿透深度、较低的溶解度、暗毒性、对氧气浓度的高度依赖等，新型的安全高效的光敏剂亟待被进一步开发，以实现高度特异性微创治疗。目前，新型光敏剂的研发主要聚焦于靶向修饰和智能纳米药物递送体系以及可激活/响应型光敏剂、耐乏氧肿瘤微环境的Ⅰ型光敏剂、适应深层实体瘤治疗的光敏剂等。此外，超声激发的声动力治疗也为光敏剂的临床应用开辟了新思路。随着新型光敏剂的开发与转化，将会有更多的光敏剂药物被应用于临床实践，为癌症和其他疾病患者带来福音。

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.

结肠癌已成为我国主要癌症发病种类之一，传统的治疗方法难以抑制其转移和复发。免疫疗法虽然可以通过机体免疫系统清除肿瘤组织，但肿瘤组织中的免疫抑制微环境，往往会导致效果不及预期。光学疗法，包括光热疗法（PTT）和光动力疗法（PDT），不仅可以直接诱导肿瘤细胞凋亡和坏死，还能改善肿瘤组织中的免疫抑制环境，从而促进免疫细胞在肿瘤组织中的浸润和活性，提高免疫治疗效果。笔者创新性地利用吲哚氰绿（ICG）介导的光学疗法和天然免疫活性分子羽扇豆醇（Lupeol）对自然杀伤（NK）细胞免疫活性的提升作用实现光-免疫协同激活作用和抗肿瘤效果，通过纳米脂质体将ICG和羽扇豆醇整合得到Lip-Lupeol & ICG，并将其用于结肠癌细胞灭活研究。结果显示：Lip-Lupeol & ICG在通过两次间隔激光照射后可实现PTT和PDT的两次治疗作用，可将结肠癌细胞活性抑制至43.4%；与此同时，包裹的羽扇豆醇释放后可与光学疗法协同激活NK细胞活性，将结肠癌细胞活性进一步抑制至16.7%，为临床结肠癌治疗提供了一种新思路。

通过水热法和表面修饰法制备了以CoFe2O4为内核、TiO2为外壳、用透明质酸修饰的HA@CoFe2O4-TiO2。利用场发射扫描电子显微镜(SEM)成像、能谱分析(EDS)、X射线衍射(XRD)、X射线光电子谱(XPS)、紫外-可见吸收光谱(UV-Vis)以及傅里叶变换红外光谱(FTIR)对复合纳米颗粒的理化性质进行表征。用细胞计数试剂(CCK-8)法研究HA@CoFe2O4-TiO2复合纳米颗粒在暗室条件下对白血病HL60细胞的毒性, 以及在光照条件下的光动力疗法(PDT)灭活效果。结合复合纳米颗粒的荧光光谱(FS)、细胞内活性氧(ROS)产量和摄取纳米颗粒水平分析, 初步探究CoFe2O4和透明质酸与TiO2结合影响PDT灭活HL60细胞的作用机制。试验结果表明, HA@CoFe2O4-TiO2形貌规则呈球形, 尺寸符合细胞摄取要求。CoFe2O4拓宽了TiO2的可见光响应范围。暗毒性试验表明, HA@CoFe2O4-TiO2复合纳米颗粒对HL60细胞的毒性较小。同时, 与TiO2和CoFe2O4-TiO2纳米颗粒相比, HA@CoFe2O4-TiO2对HL60细胞的光动力灭活效率高达82.6%, 表明其有望成为应用于体外PDT治疗白血病的光敏剂, 提高光动力效率及靶向性。

光动力疗法（PDT）是治疗各种皮肤疾病的有效手段，然而PDT过程中伴随的疼痛限制了其广泛应用。论述了PDT过程中的人体微环境变化情况，介绍了疼痛产生的机理，重点介绍了瞬时受体电位（TRP）通道对疼痛产生的影响。总结了临床缓解光动力疗法中疼痛的干预手段，比较了各措施的效果。

光动力疗法是一种利用激光、光敏剂发生光化学反应从而特异性杀灭肿瘤细胞的药械联合疗法。治疗的柔性光纤可随人体自然腔道的弯曲而弯曲，通过内窥镜活检通道，光纤能够到达腔内近距离照射肿瘤部位。内窥镜辅助光动力疗法因具有显著的局部疗效和微创治疗优势而被广泛应用于腔道恶性肿瘤的治疗中。本文介绍了光动力治疗肿瘤疾病的内窥镜技术的发展，提出了在实现术前诊断、术中可视、视场统一及诊疗一体等目标中存在的技术问题，并汇总了解决方案。本文概述了光动力诊疗内窥技术在腔道肿瘤诊疗中的临床应用现状，以期为光动力治疗的精准化发展提供参考。