基因靶向光动力治疗肿瘤

将基因治疗与靶向光动力治疗相结合，提出了“基因靶向光动力治疗肿瘤”的方法，为肿瘤治疗开辟了一条新的途径。     

肿瘤的光动力诊断和光动力治疗的研究进展

ＨＰＤ等光敏化剂可以有选择地潴留在肿瘤内，激光导出的特征光谱可用于肿瘤的光动力诊断，当用一定波和的激光照射光谱物质分子时，它可以从基态跃迁激发单态跃迁 通过系际交叉过渡到激发三重态，处于三重态的光敏化剂分子通过转移，使三重态的氧变成对肿瘤细胞具有毒化作用的单态氧，从而实现了肿瘤的光动力治疗。     

肿瘤的光动力诊断和光动力治疗的研究进展

HPD等光敏化剂可以有选择地潴留在肿瘤内，激光诱导出的特征光谱可用于肿瘤的光动力诊断。当用一定波长的激光照射光敏物质分子时，它可以从基态跃迁激发单态，通过系际交叉过渡到激发三重态。处于三重态的光敏化剂分子通过能量转移，使三重态的氧变成对肿瘤细胞具有毒化作用的单态氧，从而实现了肿瘤的光动力治疗。     

肿瘤的光动力疗法

综述了光动力疗法治疗肿瘤研究的发展过程 ,着重介绍了光动力治疗肿瘤的作用机制 ,并论述了今后的研究及发展方向。     

肿瘤导向光敏药物研究现状及发展构想

单克隆抗体偶联光敏药物介导的光动力靶向治疗肿瘤是继手术、放疗和化疗而来的肿瘤治疗方法。本文综述了抗体导向光敏药物的研究进展，并提出构建靶向光敏药物的新设想。     

谷胱甘肽响应型肿瘤治疗光敏剂的研究进展

谷胱甘肽（GSH）在多种肿瘤细胞中过表达，是肿瘤微环境的重要特征之一，以GSH作为触发因子可以实现肿瘤的精准治疗。GSH是一种内源性抗氧化剂，其分子结构中的巯基官能团能够快速消耗肿瘤细胞内的活性氧物种（ROS），降低光动力治疗（PDT）的效果；相反，GSH的消耗也可以增强PDT。因此，以GSH作为生物靶标及触发因子设计GSH响应型光敏剂有望实现高效精准的肿瘤PDT。本文首先对GSH在生物体内的作用进行了简单介绍，进而对GSH激活型和GSH消耗型光敏剂的响应机制与响应型PDT进行了详细阐述，最后对GSH响应型光敏剂在肿瘤光动力治疗中面临的挑战以及未来的发展方向进行了讨论。     

新一代光敏剂在光动力疗法中的研究进展

新一代光敏剂在光动力疗法中的研究进展操州星，唐建民（重庆第三军医大学物理教研室，６３００３８）光动力疗法（ＰｈｏｔｏｄｙｎａｍｉｃＴｈｅｒａｐｙ．ＰＤＴ）作为肿瘤治疗的新方法之一，近年来发展迅速。１９７８年，Ｄｏｕｇｈｅｒｔｙ［１］报道用血卟啉衍生物...     

光动力治疗对荷瘤小鼠肿瘤淋巴细胞表型的影响

目的:观察光动力治疗(PDT)肿瘤留置对残存肿瘤局部淋巴细胞表型的影响。方法:采用双侧小鼠荷H22移植型肝癌模型。将30只双侧荷瘤小鼠分为3组:PDT组,切除组,对照组。光动力治疗一侧肿瘤后,定量观察残存肿瘤和脾脏内CD4+和CD8+细胞的变化。使用免疫组织化学及图像分析技术。结果:在原位肿瘤内,有极少量的CD4+细胞。在残存肿瘤内,未见CD4+细胞,CD8+细胞呈明显的带状分布,在光动力治疗组,CD8+细胞的密度明显增高,但仍不足以杀死残存肿瘤,其活性也有待进一步研究。     

用于肿瘤治疗的光动力疗法

本概述了光动力疗法的基本原理、光源和光波长的选择及光剂量的计算，介绍了基于ALA的PDT的原理及血红素的合成过程，并阐述了PDT在肿瘤治疗方面的应用。     

腔道肿瘤光动力诊疗内窥技术的发展及临床应用现状

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。     

400mW氦氖激光器及其在光动力学治疗上的应用

一种高功率氦氖激光器采用两只扁平放电截面氦氖激光管，其输出功率可达４００ｍＷ，经光学系统耦合单股石英光纤输出，作光动力学治癌用。经４４例临床治疗，总治愈率可达６０％，本文还简要讨论了不同激光光源作光动力学治癌疗效差异机制等问题。     

Nd:YAG激光与光动力学疗法联合治疗直肠肛管癌

应用NdYAG激光与光动力学疗法联合治疗直肠肛管癌21例,有效率为95.2%,结果表明两种的联合应用可使疗效提高,疗程时间缩短,并防止并发症,对疗效及治疗的机理进行了讨论.     

Enhanced Antitumor Efficacy by 808 nm Laser‐Induced Synergistic Photothermal and Photodynamic Therapy Based on a Indocyanine‐Green‐Attached W18O49 Nanostructure

A novel nanoplatform based on tungsten oxide (W₁₈O₄₉, WO) and indocyanine green (ICG) for dual‐modal photothermal therapy (PTT) and photodynamic therapy (PDT) has been successfully constructed. In this design, the hierarchical unique nanorod‐bundled W₁₈O₄₉ nanostructures play roles in being not only as an efficient photothermal agent for PTT but also as a potential nanovehicle for ICG molecules via electrostatic adsorption after modified with trimethylammonium groups on their surface. It is found that the ability of ICG to produce cytotoxic reactive oxygen species for PDT is well maintained after being attached on the WO, thus the as‐obtained WO@ICG can achieve a synergistic effect of combined PTT and PDT under single 808 nm near‐infrared (NIR) laser excitation. Notably, compared with PTT or PDT alone, the enhanced HeLa cells lethality of the 808 nm laser triggered dual‐modal therapy is observed. The in vivo animal experiments have shown that WO@ICG has effective solid tumor ablation effect with 808 nm NIR light irradiation, revealing the potential of these nanocomposites as a NIR‐mediated dual‐modal therapeutic platform for cancer treatment.     

Red Blood Cell‐Facilitated Photodynamic Therapy for Cancer Treatment

Photodynamic therapy (PDT) is a promising treatment modality for cancer management. So far, most PDT studies have focused on delivery of photo­sensitizers to tumors. O₂, another essential component of PDT, is not artificially delivered but taken from the biological milieu. However, cancer cells demand a large amount of O₂ to sustain their growth and that often leads to low O₂ levels in tumors. The PDT process may further potentiate the oxygen deficiency, and in turn, adversely affect the PDT efficiency. In the present study, a new technology called red blood cell (RBC)‐facilitated PDT, or RBC‐PDT, is introduced that can potentially solve the issue. As the name tells, RBC‐PDT harnesses erythrocytes, an O₂ transporter, as a carrier for photosensitizers. Because photosensitizers are adjacent to a carry‐on O₂ source, RBC‐PDT can efficiently produce ¹O₂ even under low oxygen conditions. The treatment also benefits from the long circulation of RBCs, which ensures a high intraluminal concentration of photosensitizers during PDT and hence maximizes damage to tumor blood vessels. When tested in U87MG subcutaneous tumor models, RBC‐PDT shows impressive tumor suppression (76.7%) that is attributable to the codelivery of O₂ and photosensitizers. Overall, RBC‐PDT is expected to find wide applications in modern oncology.     

A Bioactive Photosensitizer for Hypoxia-Tolerant Molecular Targeting-Photo-Immunotherapy of Malignant Tumor

Photosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment of malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency of photodynamic therapy (PDT). Herein, a molecular-targeting photosensitizer QTANHOH is rationally designed for histone deacetylases (HDACs-targeting photo-immunotherapy application. The PS QTANHOH displays excellent type-I/II PDT performance, exhibiting significant phototoxicity toward cancer cells with half maximal inhibitory concentration (IC₅₀) less than 10 nm in both normoxia and hypoxia conditions under blue laser irradiation. Moreover, the bioactive compound could inhibit HDACs and activate the immune microenvironment to boost PDT efficacy on the immunocompetent BALB/c mice with breast cancer, leading to the eradication of solid tumor and inhibition of metastasis. Notably, the molecular-targeting photosensitizer introduces an alternative strategy to achieve superior phototherapy for cancer therapy.     

Photodynamic therapy of human cancer

Photodynamic therapy (PDT) is currently an investigational therapy for human cancer. PDT is performed in two steps: (a) the injection of a photosensitizer, followed by a period of time during which it is cleared from most normal tissues; and (b) activation of the photosensitizer by exposure to light. Singlet oxygen is thought to be the agent produced by photoactivation most responsible for tumor destruction. Over 3000 patients have been treated with PDT and reported in the literature. The published results of clinical PDT in the treatment of superficial bladder cancer, gynecological cancer, endobronchial malignancies, gastrointestinal cancer, intracranial cancer, ocular cancer, and cutaneous and subcutaneous cancers are critically reviewed in the present work. The current laser types used for clinical PDT are reviewed, as well as light delivery devices which have been recently developed. In situ light dosimetry devices and their use in the treatment of superficial bladder cancer and for intraoperative therapy are discussed     

光动力疗法对Louis肺癌鼠的杀伤及免疫效应

应用光动力疗法对 30只接种Louis肺癌瘤株的昆明小鼠作杀伤实验研究。对实验组与对照组荷瘤鼠抑瘤曲线、抑瘤率及免疫学指标进行检测。结果表明 ,两组肿瘤生长曲线存在明显差异 (P<0 0 5 )。两组肿瘤生长体积和肿瘤重量均存在明显差异 (P <0 0 1)。实验组瘤体积抑制率为 5 2 94 % ,瘤重量抑制率为 37 2 4 %。各免疫指标与对照组差异有显著性。说明光动力疗法对肿瘤细胞具有杀伤和抑制生长作用 ,并且对荷瘤小鼠的免疫功能有调节作用     

Hyperbranched Polyglycerol‐Doped Mesoporous Silica Nanoparticles for One‐ and Two‐Photon Activated Photodynamic Therapy

Two‐photon activated photodynamic therapy (TPA‐PDT) is a recently developed technique that shows a potential for medical application. In contrast to traditional one‐photon activated PDT, TPA‐PDT can increase the treatment depth and decrease the damage to healthy tissue by using a near‐infrared two‐photon laser. However, this technique also suffers from the fact that approved photosensitive drugs have a low two‐photon absorption cross section. In this study, it is demonstrate that doped polyglycerol mesoporous silica nanoparticles can carry a photosensitizer, Rose bengal, and can be applied in one‐ and two‐photon PDT. TPA dye‐doped mesoporous silica nanoparticles have been synthesized using a surfactant‐free route, which can be considered a TPA‐PDT platform after loading normal photosensitive drugs. The doped TPA dyes in the silica nanoparticles can transfer energy to the loading drugs via an intraparticle fluorescence resonance energy transfer (FRET) mechanism. The fluorescence lifetime and confocal laser scanning microscopy (CLSM) images obtained under different conditions demonstrated a FRET effect through both one‐ and two‐photon activated modes. The results of cytotoxicity experiments proved that this TPA‐PDT system could induce cellular apoptosis under one‐ or two‐photon irradiation. This system in principle extends the application range of TPA‐PDT.     

光动力疗法对巨噬细胞作用研究进展

光动力疗法(Photodynamic Therapy,PDT)是指利用光敏剂在病变组织内聚集,在特定的波长的光或者激光的照射下被激活,产生单态氧或者其他自由基,造成病变组织坏死,不损伤正常组织的疗法[1]。这些年来,PDT已经得到了广泛的应用,越来越多的研究者开始关注着它的机制。近年来许多研究发现PDT对巨噬细胞吞噬活性及其极化具有重大作用。本文就拟对PDT对巨噬细胞的作用及机制进行阐述。     

A Self‐Transformable pH‐Driven Membrane‐Anchoring Photosensitizer for Effective Photodynamic Therapy to Inhibit Tumor Growth and Metastasis

Poor tumor selectivity and short life span of reactive oxygen species (ROS) are two major challenges in photodynamic therapy (PDT). In this study, a self‐transformable pH‐driven membrane anchoring photosensitizer (pHMAPS) is used to realize tumor‐specific accumulation and in situ PDT on tumor cell membrane to maximize the therapeutic potency. It is found that pHMAPS was able to form α‐helix structure under acidic condition (pH 6.5 or 5.5), while remain random coil at normal pH of 7.4. This pH‐driven secondary structure switch enables the successful insertion of pHMAPS into membrane lipid bilayer, especially for cancerous cell membrane in the acidic tumor microenvironment. Under laser irradiation, cytotoxic ROS is generated in the immediate vicinity of cell membrane, resulting in superior cell killing effect in vitro and significant inhibition of tumor growth in vivo. Importantly, benefited from this membrane‐specific PDT, tumor growth‐induced hepatic, pulmonary, as well as osseous metastases of breast cancer cells are also retarded after PDT treatment. Thus, the membrane localized PDT by pHMAPS provides a simple but effective strategy to enhance the medical performance of photosensitizing agents in cancer therapy.