光敏剂与光动力学疗法

与传统疗法作用方式不同,光动力学疗法是通过光敏剂、光和分子氧在病灶区联合产生的理化作用诱生的生物效应实现治疗目的。光动力学疗法是在光敏剂的发现和发展以及医用激光光源的发展推动下发展起来的。了解和掌握光动力学疗法的发展,必须先要了解光敏剂和光源的发展,作者结合光敏剂的发展简述光动力学疗法的发展和现状。从发现吖啶橙和血卟啉的光动力损伤作用到制得血卟啉衍生物(HpD)及随之发现其对肿瘤组织的光动力损伤作用,奠定了肿瘤光动力学疗法的基础。上世纪70年代,肿瘤临床HpD-光辐照治疗的成功揭开了人类肿瘤防治新技术—光动力…     

肿瘤光动力疗法——作用机制

肿瘤光动力疗法（Photodynamic therapy,PDT）是一种应用于实体肿瘤治疗的新方法。机体被施予光敏剂后,再用特定波长的光照射,光敏剂随之活化,与底物及氧分子作用产生单线态氧及其他活性氧物质,可以直接杀伤肿瘤细胞。此外,其他作用如血管损伤、诱发炎症反应、促进抗肿瘤免疫等亦可导致肿瘤细胞死亡。本文综述了光动力疗法在肿瘤治疗方面的作用及其机制。     

光动力治疗三要素及肿瘤光动力治疗后复发问题的探索

光动力疗法(photodynamic therapy,PDT)是一种联合利用光敏剂、光和氧,通过光动力反应选择性地治疗肿瘤的局部靶向疗法。光敏剂、激光和氧是光动力疗法的三个重要元素,本文主要从PDT的三要素及PDT后肿瘤复发进展的原因进行了综述。     

光动力作用与生物膜

光动力学疗法(photodynamic therapy，PDT)是一种细胞毒性治疗方法，它能引起细胞凋亡或坏死，已经应用于瘤性和非瘤性疾病的治疗。PDT需要有光敏剂、光、分子氧的参与。还必须有受作用的物质，这些是正常或异常结构中的一些生物物质，也可以是细胞代谢产物，甚至是氧化形成的毒性物质，但主要是蛋白质、酶和核酸等生物大分子。光敏剂的细胞内定位是光动力作用的关键，光敏剂定位在线粒体可快速诱导细胞凋亡，定位在溶酶体诱导细胞凋亡或坏死。细胞膜和细胞内膜统称为生物膜，是光动力作用诱导细胞氧化破坏非常重要的部位。膜的氧化破坏包含许多不同的机制和膜组分。细胞对光动力作用的反应，因所使用的光敏剂、光照条件、组织氧合状态及所处理的细胞种类的不同而异。本文主要就光动力作用对细胞生物膜的影响作一综述。     

光动力抗菌疗法治疗牙周炎的研究进展

牙周炎是发生于牙齿支持组织的炎症性疾病,是造成成人牙齿丧失的主要原因。菌斑生物膜是牙周病的主要致病因素。牙周治疗目的在于去除致病因素,消除牙周组织的感染。目前控制菌斑生物膜的方法主要是机械清除法和化学药物法,但两者皆有其局限性。光动力抗菌疗法是利用激活的光敏剂将能量传递给可利用的氧,生成单线态氧和自由基等有毒性的氧物质,破坏细胞的蛋白质、脂质、核酸及其他成分以达到杀灭致病菌的方法。光动力抗菌疗法主要涉及光敏剂、光源和氧,其中光敏剂是核心物质。本文就光动力抗菌疗法在牙周病治疗中的应用现状作一综述。     

光动力疗法的基础研究新进展

<正>光动力疗法(photodynamic therapy,PDT)是一种联合利用光、光敏剂和氧分子,通过光动力反应选择性地治疗肿瘤,以及湿性老年性黄斑变性和鲜红斑痣等良性疾病的新疗法。PDT是作为生物医学光子学中的一个重要研究方向,本文重点总结并分析了国内外近年来PDT在新型光敏剂和光源、细胞和生物作用机制,氧分压检测,以及临床剂量学等基础研究领域的最新进展。     

非手术的浅表食管癌患者放化疗后光动力疗法治疗的严重并发症发生率高于单纯光动力治疗

背景与目的 光动力疗法是一种治疗浅表食管癌的有效方式,有效率为75％一80％。这种方法通过激光激发光敏剂,产生单线态氧,选择性的破坏肿瘤组织。光动力疗法治疗可用于不适合外科手术的浅表食管癌,也可用于曾行黏膜或黏膜下切除的浅表食管癌患者,还可用于放化疗后的局部复发病灶。光动力疗法治疗浅表食管癌的有效性及并发症的发生率尚未被研究。本实验的研究目的是比较浅表食管癌患者在放化疗后与单纯光动力疗法治疗的有效性及安全性。     

影像导航的光动力肿瘤治疗方法

目的:光动力疗法(Photodynamic Therapy,PDT),是以光、光敏剂和氧的相互作用为基础的一种新的疾病治疗手段,已成为世界肿瘤防治科学中最活跃的研究领域之一。PDT的理论基础是某些特定的、具有靶向性作用的药物(光敏剂)进入患者体内后,动态聚集于生长异常的肿瘤组织中,选择特定波长的激光照射使组织中的光敏剂受到激发,生成     

光漂白对光动力疗法选择性的影响以及光漂白的机制

光漂白是光敏剂的重要性质,是光动力疗法治疗中的普遍现象,在光动力疗法治疗肿瘤和血管疾病中有利有弊.笔者总结了国内外文献对不同光敏剂光漂白机制和光漂白对光动力疗法选择性影响的论述.     

荧光显微成像技术在光敏剂亚细胞定位及损伤研究中的应用

一、光动力学疗法的基本原理及光敏剂亚细胞定位研究的重要意义光动力疗法(photodynamictherapy,PDT)是指静脉或局部给予光敏剂,应用可见光或近红外光照射后吸收光子能量,在有氧状态下传递能量,产生对细胞有毒性的物质如单线态氧和其他氧自由基犤1犦。这些物质能和细胞内成分发生反应而造成细胞损伤。激发态单态氧寿命极短,在细胞内扩散不超过10～20nm。因此,靶细胞光动力损伤主要位点和光敏剂的亚细胞分布紧密相关犤2犦。研究发现由于细胞光敏损伤位点不同,其损伤特点及后果也不同犤3犦。一般认为,光动力作用引起细胞内线粒体损伤使靶细…     

光动力治疗与细胞自噬的研究进展

细胞自噬是真核生物中一种发现不久的普遍存在的生理现象,是涉及细胞自我消化的一系列生化过程。光动力治疗（photodynamic therapy,PDT）中,选择性聚集在快速增殖细胞（如肿瘤细胞）中的光敏剂分子经一定波长激光照射,产生有细胞毒作用的单态氧或氧自由基,靶向性地杀伤肿瘤细胞,引起肿瘤细胞死亡。PDT作用过程能够诱发一些细胞器如内质网、线粒体、细胞膜和溶酶体的损害,进而引起细胞凋亡和自噬的发生。对于一些接受低水平剂量的光动力作用细胞,其发生的自噬被认为与提高细胞在应激环境下的生存有着密切联系。然而,当凋亡受到抑制或是自噬水平无限制的持续上调时,自噬就成为了细胞死亡的一种途径。目前很多相关的实验技术已运用来检测细胞自噬的特征,本文就针对光动力治疗后引起自噬的一些相关问题做一详细综述。     

Multifunctional nanoplatform based on g-C3N4, loaded with MnO2 and CuS nanoparticals for oxygen self-generation photodynamic/photothermal synergistic therapy

Photodynamic therapy (PDT) and photothermal therapy (PTT) are both promising therapeutic approaches for cancer. Unfortunately, the anticancer efficiency of PDT is restricted by the hypoxic tumor microenvironment and the performance of the photosensitizer (PS) while the efficiency of PTT is limited by the penetration depth of NIR light, making it difficult to further improve the efficiency of the treatment. In this paper, we strategically proposed a multifunctional nano-platform based on g-C₃N₄ and loaded with CuS and MnO₂ nanoparticals. Interestingly, the obtained F127@CNs-CuS/MnO₂ nano-platform with high singlet oxygen quantum yield and excellent photothermal performance were used in synergistic PTT and PDT therapy to cope with the limitation of single mode cancer treatment under irradiation and has greatly improved the treatment effect. Additionally, MnO₂ nanoparticles loaded on the CNs surface could not only generate oxygen to ameliorate hypoxia in the tumor environment by reacting with H₂O₂ in tumor cells, but also react with the over-expressed reduced glutathione (GSH) in cancer cells to further improve the synergistic therapeutic effect. In the in vitro hepatocarcinoma cell inactivation experiment, the maximum cell inactivation efficiency of the PDT, PTT and PDT/PTT synergistic treatment group reached at 65% (F127@CNs-MnO₂), 69.2% (CNs-MnO₂) and 88.6% (F127@CNs-MnO₂) respectively, which means that the F127@CNs-CuS/MnO₂-mediated PTT/PDT synergy anticancer treatment was more effective than single mode therapy. In summary, the innovative multifunctional nanoplatform F127@CNs-CuS/MnO₂ used for synergistic PTT and PDT treatment has greatly improved the inactivation efficiency of cancer cells and has provided a new scheme for the treatment of hypoxic tumors.     

Carbon nitride nanomaterials with application in photothermal and photodynamic therapies

Phototherapies offer treatment of tumors with high spatial selectivity. Photodynamic therapy (PDT) consists in the administration of a photosensitizer (PS) followed by local photoirradiation with light of specific wavelength. The excited states of the PS interact with biomolecules and molecular oxygen producing reactive oxygen species (ROS), which initiate cell death. Photothermal therapy (PTT) employs photothermal agents to harvest the energy from light and convert it into heat to produce a temperature increase of the surrounding environment leading to cell death.Due to their good biocompatibility and unique photophysical properties, carbon-based materials are suitable for application in PDT and PTT. In particular, graphitic carbon nitride (g-C₃N₄), is a low-cost, non-toxic, and environment-friendly material, which is currently being used in the development of new nanomaterials with application in PDT and PTT.This brief review includes recent advances in the development of g-C₃N₄-based nanomaterials specifically designed for achieving red-shifted band gaps with the aim of generating oxygen molecules via water splitting upon red light or NIR irradiation to tackle the hypoxic condition of the tumor area. Nanomaterials designed for theranostics, combining medical imaging applications with PDT and/or PTT treatments are also included. The recent developments of g-C₃N₄-nanomaterials containing lanthanide-based upconversion nanoparticles are also covered. Finally, g-C₃N₄-based nanomaterials employed in microwave induced photodynamic therapy, sonodynamic therapy, and magnetic hyperthermia are considered.     

光动力疗法中组织氧的测量技术

光动力疗法（photodynamic therapy,PDT）是一种联合利用光敏剂、光和氧,通过光动力反应选择性地治疗疾病的靶向疗法。氧作为PDT的关键要素之一,直接决定毒性物质单态氧和其他活性氧的产量,进而影响PDT的疗效。PDT中组织氧的在体和实时监测是一个具有挑战性的技术难题,在过去的20年中,基于不同原理的各种组织氧的测量技术被相继开发和应用。笔者在阐述PDT中氧的作用机制基础上,详细讨论组织氧的直接和间接测量技术,分析各种测量技术的优点和局限性,展望组织氧测量技术在优化PDT治疗方案和评估疗效中的应用,简要评述面临的技术挑战。     

Enhanced efficacy of PDT when combined with nitroglycerin ointment administration on xenografted retinoblastoma in mice.

The aim of the study was to assess the efficacy of a treatment protocol that combines photodynamic therapy (PDT) and nitroglycerin (NG) on human retinoblastoma tumors xenografted on nude mice.PDT uses a non-mutagen photosensitizing agent (PS: glycoconjugated porphyrin derivative) activated by red light exposure. Absorption of light initiates photochemical reactions leading to the generation of cytotoxic photoproducts (ROSs: oxygen reactive species) responsible for the therapeutic effects [1]. We propose to increase the PDT efficiency (on our least responsive retinoblastoma line to treatment) with a better PS delivery in the tumor generated by NG which is known to dilate vessels and enhance the permeability and retention of macromolecules in solid tumors [2].Methods: In vivo follow-up of the therapeutic effects was performed by sodium MRI which directly monitors variations of sodium concentrations in a non-invasive way and can be used to follow-up the tumor response to therapy [3]. NG ointment was applied one hour before PDT. The PDT protocol implied a double tumor targeting, cellular and vascular. A first PS dose was injected followed by a second one, separated by a 3 h interval. The time lapse allowed the PS molecules to penetrate into tumor cells. Ten minutes after the second dose, the PS was red light activated.Results: The PDT efficacy (increase of necrosis, decrease of the tumor volume) was enhanced by applying NG ointment on the skin of tumor-bearing animals.Conclusion: NG increases the PDT efficacy by enhancing the intratumor concentration of PS inducing a more significant production of ROSs on the illuminated region increasing thus the propagation of cellular death signalling deeper into the tumor (bystander effect).     

Pulse mode of laser photodynamic treatment induced cell apoptosis

One of the factors limiting photodynamic therapy (PDT) is hypoxia in tumor cells during photodynamic action. PDT with pulse mode irradiation and appropriate irradiation parameters could be more effective in the singlet oxygen generation and tissue re-oxygenation than continuous wave (CW) mode. We theoretically demonstrate differences between the cumulative singlet oxygen concentration in PDT using pulse mode and CW mode of laser irradiation. In vitro experimental results show that photodynamic treatment with pulse mode irradiation has similar cytotoxicity to CW mode and induces mainly cell apoptosis, whereas CW mode induces necrotic cell death. We assume that the cumulative singlet oxygen concentration and the temporal distribution of singlet oxygen are important in photodynamic cytotoxicity and apoptosis initiation. We expect our research may improve irradiation protocols and photodynamic therapy efficiency.     

Structure-function analysis of Squaraines phototherapeutic activity: in vitro characterization of ROS and intracellular Ca2+ signals interplay in phototoxicity

Photodynamic therapy (PDT) is an emerging, minimally invasive therapeutic modality approved by the U.S Food and Drug Administration for the treatment of several conditions including oncological applications ¹. The approach is based on light-induced photosensitizers (PS) activation which, in turn, promotes the intersystem crossing and triplet state that easily reacts with molecular oxygen, thus generating free radicals and singlet oxygen species which in turn involve intracellular Ca2+ signals as well as other messengers with a final increase in apoptosis, necrosis, and autophagy processes and tumor mass reduction ^1,2. In this context, the development of new PS for the PTD is of great interest to increase the treatment efficacy minimizing side effects^3,4.In the present work, we investigated the structure-functional role of SQ by comparing the phototoxic activity of unsubstituted SQ, carboxyl (COOH)- and bromine (Br)-substituted SQ, as well SQ in which the oxygen atoms of the squaryl ring were replaced with sulfur atoms (S-SQ). Indeed, the presence of heavy atoms such as Br and the replacement of oxygen with sulfur are predicted to shift the emission to the far NIR region and increase the quantum yield of singlet oxygen, thus improving the overall effect in PDT. As expected, Br-SQ and S-SQ demonstrate a higher phototoxicity on MCF-7 cells compared to the COOH-SQ dye, which showed no effect. However, surprisingly, our data reveal that also the unsubstituted SQ has a strong phototoxic activity. To deeper analyze the the molecular mechanisms underlying SQ phototoxicity, we studied the role of Ca2+ signals and ROS generation in light induced PS activation. Our results clearly show that Br-SQ promote ROS production as well as significant increase in cytosolic Ca2+ signals mainly due to Ca2+ release form ER stores which in turn promotes a sustained Ca2+ uptake in the mitochondria while no effect was observed for the COOH-SQ. Our results shed new light on the structure-function relationship of SQ and the intracellular pathways involved in their exploitable photo-activity in PDT, demonstrating a critical role for intracellular Ca²⁺ signals in ROS activation and cell death.     

光动力疗法合并化学疗法治疗恶性肿瘤的实验研究

我们对人癌ＨｅＬａ细胞株的裸鼠接种瘤进行了光动力疗法（ＰＤＴ）联合应用肿瘤ＤＮＡ合成酶抑制剂，目的在于探讨增强ＰＤＴ作用的有效途径。观察到在本实验条件下，仅做激光照射或单纯采用抗癌剂，对这种移植癌均无抗肿瘤作用；ＰＤＴ组的肿瘤生长阻止率为３５．１％～４７．９％，而ＰＤＴ并用化疗组的肿瘤生长阻止率达８０％～９５％。研究表明，ＰＤＴ合并应用化学疗法比单独实施ＰＤＴ对抑制肿瘤生长、破坏肿瘤组织的效应显著     

In vivo and in vitro models for photodynamic therapy by using novel photosensitizers

Photodynamic therapy (PDT) is an effective treatment for both malignant and non-malignant diseases, and new photosensitizers / chromophores are studied by confocal imaging and biological techniques determining cell survival with/without light. During PDT the activated PS transfers energy to nearby oxygen molecules, generating singlet oxygen (¹O₂) resulting in oxidative stress (ROS), which further elicit cell death by necrosis and apoptosis. Protoporphyrin IX (PpIX), is an efficient and widely used PS for bladder superficial bladder cancer treatment; either endogenously produced in the cancer cells by e. g. aminolaevulinic acid (ALA) or exogenously added as e. g. hexyl-ALA. The effects in vitro and in vivo are present by using an orthotopic rat cancer model; also included pphotochemical internalization (PCI). This is a new strategy for local enhancement of various types of drug molecules by employing a photosensitising compound and illumination of a diseased area in the body. The possibility of using PCI to enhance effects of the cytotoxic drug bleomycin is investigated, together with photophysical determinations and outlines of a treatment for intravesical therapy of bladder cancer. In vitro experiments indicate that employment of PCI technology using the novel photosensitizer TPCS_2a® enhance cytotoxic effects of bleomycin in bladder cancer cells. Furthermore, experiments in an orthotopic in vivo bladder cancer model show effective reduction in both necrotic area and bladder weight after TPCS_2a based photodynamic therapy (PDT). The tumor selectivity and PDT effects may be sufficient to destroy tumors without damaging detrusor muscle layers. Our results present a possible new treatment strategy for non-muscle invasive bladder cancer, with intravesical instillation of photosensitizer and bleomycin followed by illumination through an optic fiber by using a catheter.     

Brain extracellular matrix attenuates photodynamic cytotoxicity of glioma cells

Glioma is the most common tumor in the central nervous system, which is often accompanied by poor prognosis. Brain extracellular matrix (ECM) plays an important role in regulating the growth and migration of glioma. Photodynamic therapy (PDT) has been an effective method for the treatment of solid tumors by oxidative modifications in recent years, and ECM may have an impact on the cytotoxicity of photodynamic therapy. In this work, we prepared decellularized brain ECM by chemical method to investigate the influence of the photodynamic effect of glioma C6 cells. Compared with decellularized liver ECM, brain ECM reduces PDT cytotoxicity. By observing the content of reactive oxygen species produced by near-infrared light active indocyanine green in cells, it was found that ECM did not affect the production of reactive oxygen species. Therefore, it is speculated that brain ECM may enhance the oxidative stress adaptability of glioma cells through potential signal regulation, or protect photodynamic targeting biomolecules (such as proteins and other cellular components) from oxidation in PDT mediated by indocyanine green and 808 nm laser in glioma cells.