Palladium-substituted bacteriochlorophylls for photodynamic therapy

This patent concerns the preparation of a series of palladium substituted bacteriochlorophyll derivatives as photosensitisers (PSs) and their potential use in the field of photodynamic therapy. Remarkably, the proposed compounds present a substituent capable of allowing an efficient plasma transfer and good cell membrane penetration. A number of interesting in vitro and in vivo biological actions of the principal compound Pd- bacteriopheophorbide are described. This patent contributes to the repertoire of compounds with potential application in photodynamic therapy (PDT).     

光动力治疗过程中的疼痛和缓解对策

目的：调查光动力治疗（photodynamic therapy,PDT）过程中疼痛的相关影响因素,以及缓解疼痛的有效方法。方法：在PubMed数据库中检索PDT过程中疼痛的临床研究文献,并对数据进行总结。结果：治疗过程中的疼痛是PDT最常见的不良反应。与疼痛相关的因素包括光敏剂类型、病损部位和大小、辐照剂量、光源类型和波长等。多种疼痛缓解对策已经被研究,大多数研究显示,外用局麻药物对缓解PDT疼痛无效。对治疗部位冷却能部分缓解PDT疼痛,但效果是不充分的。神经阻滞可以有效地缓解PDT疼痛。结论：治疗部位冷却是缓解PDT疼痛,提高患者耐受度最简单、最经济的方法,作为临床优先方案被推荐使用。对于简单冷却效果不佳的患者,可以选择神经阻滞来有效控制PDT过程中的疼痛。     

Photodynamic Therapy of Skin Cancers: Sensitizers,Clinical Studies and Future Directives

Photodynamic therapy (PDT) is a new modality of skin cancer treatment. It involves the administration of photosensitizing drugs which, when localized in tumor tissue can produce its destruction by absorbing an adequate dose of light of an appropriate wavelength. A large number of photosensitizing agents have been tested in PDT experiments. Topical application of 5-aminolevulinic acid (5-ALA) followed by light irradiation is the most commonly used method. 5-ALA is a prodrug converted in situ via the heme cycle into protoporphyrin IX, an effective photosensitizer agent. Treatment of nonmelanoma skin cancers by PDT has met with varying degrees of success. In the case of 5-ALA, this therapy's main limitation is the poor penetration of 5-ALA into skin, due to hydrophilic and charge characteristics. However, the efficacy of 5-ALA-PDT may be improved by (a) development of adequate drug delivery systems; (b) use of enhancers of PpIX production and accumulation in target tissue, and (c) modifications of the 5-ALA molecule. Optimal timing, light sources, doses, and number of applications are also important factors for topical 5-ALA therapy and must be well defined. The aim of this review is to highlight recent progress in 5-ALA-PDT of skin cancer, and to present ways holding promise for its improvement.     

纳米材料在癌症光动力治疗研究中的应用进展

纳米材料以其明确的大小、形状、组成和表面能等性能为生物分析、生物成像和治疗提供了多模式、多功能的平台。本文重点综述了多种纳米技术在光动力疗法治疗癌症方面的应用进展,包括上转换纳米粒、量子点、纳米金、碳纳米材料、二氧化硅纳米粒、脂质体和胶束纳米材料,对各种纳米材料的特点以及近些年来相关研究和发展情况进行了评述。     

Verteporfin ocular photodynamic therapy

This article reviews the pharmacotherapeutics of verteporfin (Visudyne^®, Novartis Pharma AG) used in ocular photodynamic therapy. The chemistry, pharmacokinetics and pharmacodynamics of the drug are reviewed. The article highlights and summarises the results of the multi-centre, randomised, controlled clinical trials with verteporfin to treat subfoveal choroidal neovascularisation in age-related macular degeneration, ocular histoplasmosis syndrome and pathologic myopia. In addition, the safety profile and side effects of verteporfin are discussed.     

5-氨基酮戊酸光动力疗法在尖锐湿疣治疗中的应用进展

尖锐湿疣是由人乳头瘤病毒（HPV）感染所引起的良性上皮肿瘤,性接触是其主要传播途径之一。目前尚没有非常理想的治疗药物与技术,传统的激光、冷冻等创伤性治疗给患者带来痛苦,且复发率高,部分特殊部位无法对其治疗。光动力疗法是一门新兴的消融技术,并在2009年被正式列入美国疾病控制和预防中心（CDC）制定的＂性病治疗指南＂。近年来5-氨基酮戊酸光动力疗法治疗尖锐湿疣的疗效已获得了普遍的肯定。本文就光动力疗法在尖锐湿疣治疗中的应用进展进行综述。     

5-氨基酮戊酸光动力疗法在尖锐湿疣治疗中的应用进展

尖锐湿疣是由人乳头瘤病毒(HPV)感染所引起的良性上皮肿瘤,性接触是其主要传播途径之一.目前尚没有非常理想的治疗药物与技术,传统的激光、冷冻等创伤性治疗给患者带来痛苦,且复发率高,部分特殊部位无法对其治疗.光动力疗法是一门新兴的消融技术,并在2009年被正式列入美国疾病控制和预防中心(CDC)制定的"性病治疗指南".近年来5-氨基酮戊酸光动力疗法治疗尖锐湿疣的疗效已获得了普遍的肯定.本文就光动力疗法在尖锐湿疣治疗中的应用进展进行综述.     

磺酸基邻苯二甲酰亚氨甲基酞菁锌C光动力效应诱导肿瘤细胞凋亡

目的：研究新型光敏剂磺酸基邻苯二甲酰亚胺甲基酞菁锌Ｃ光动力效应诱导肿瘤细胞凋亡,探索其光动力杀伤机理,方法：用ＡＯ／ＥＢ荧光染色法,流式细胞仪及电子显微镜观察该光敏剂光动力效应与人白血病Ｋ５６２细胞形态,超微结构及ＤＮＡ含量的影响,结果：药物作用２ｈ,以红外照射后继续培养３ｈ以上,就可出现明显的细胞凋亡特性征改变。结论：新型光敏剂磺酸基邻苯二甲酰亚氨甲基酞菁锌Ｃ光动力杀伤作用与诱导肿瘤细胞凋亡有关     

<Emphasis Type="Italic">In Vitro</Emphasis> Metabolism of 5-ALA Esters Derivatives in Hairless Mice Skin Homogenate and <Emphasis Type="Italic">in Vivo</Emphasis> PpIX Accumulation Studies

No HeadingPurpose. In topical photodynamic therapy, 5-ALA and its esters are enzymatically converted in the endogenous photosensitizing compounds such as, for example, protoporphyrin IX (PpIX). In order to elucidate in more detail their enzymatic fate, we have determined in vitro the enzymatic degradation of methyl, butyl, hexyl, and octyl-5-ALA ester derivatives in skin homogenate. Furthermore, in vivo porphyrin accumulation was measured in healthy hairless mice skins.Methods. Hairless mouse skins were homogenized in isotonic phosphate buffer pH 7.4. 5-ALA esters were added, and aliquots were colleted for HPLC-fluorimetric determinations of remaining content of 5-ALA esters. Furthermore, oil-in-water emulsions containing esters were topically applied to mice skin for 6 h, and the amount of accumulated PpIX in the treated areas was determined by quantitative extraction and confocal fluorescence microscopy.Results. The enzymatic degradation of esters follows pseudo first-order kinetics. The octyl ester had the largest rate constant for enzymatic degradation, followed by hexyl-, butyl-, and methyl-ALA. The long-chained 5-ALA esters, butyl-, hexyl-, and octyl ester, induced significantly more porphyrins than 5-ALA and 5-ALA methyl ester as shown by confocal microscopy and quantitative extraction studies.Conclusions. 5-ALA derivatives differ widely with respect to their enzymatic degradation. The presence of alkyl chains in 5-ALA esters significantly influences the in vitro enzymatic metabolism and the in vivo PpIX formation in healthy hairless mice skins.     

Current strategies for DNA therapy based on lipid nanocarriers

Introduction: Lipid based nanocarriers represent one of the most widely used strategies for the delivery of gene molecules. This review focuses on current strategies for the use of these nanocarriers that could open new horizons in DNA therapy and offer an opportunity to support the transition from resource-based approaches towards knowledge-based strategies.

Areas covered: The present review highlights the most promising approaches focusing on the development of safe, stable, and effective lipid-based carriers capable of delivering DNA to the proper target sites and cells. In addition, we intend to provide some insights in to future strategies that should be considered in order to break down barriers in the transformation of DNA basic-science breakthroughs into clinical applications.

Expert opinion: On the basis of the significant advances in the design of lipid nanocarriers our impression is that they are, with respect to other systems, in a ‘pole’ position in the DNA therapy development race.     

基于新型光敏剂的光动力治疗在胆管癌中的应用

目的：验证新型叶绿素类光敏剂———2-1-己氧乙基-2-去乙烯基卟吩e6三钠盐（ HCE6）,光动力疗法对于QBC939系胆管癌细胞的光动力治疗作用,并探讨其量效关系。方法 CCK-8检测652 nm不同激光光强度下不同浓度（0、0．3、0．5、1．0、15、2．0 mg· L－1）光敏剂HCE6光动力处理下细胞的增殖率,得出最适光动力剂量。建立QBC939系胆管癌细胞荷瘤裸鼠模型,光敏剂尾静脉注射0．5 mg· kg－1,24 h后接受激光治疗（激光剂量：120 J· cm－2,功率0．2 W,治疗20 min）,激光治疗后1、3、5、7、10 d观察实验组和对照组瘤体体积变化差异,并对比观察瘤体病理变化。结果在最适光照强度2．7 J· cm－2（功率0．9 W,PDT处理5 min）剂量,随着光敏剂浓度升高,细胞增殖率逐渐下降,最适完全抑制浓度为1．5 mg· L－1;超过这个浓度,细胞增值率变化无差异。荷瘤裸鼠模型实验中实验组和对照组有明显肿瘤体积差异（P＜0．05）,光动力治疗第10天,实验组与对照组体积差异明显（P＜0．05）,实验组瘤块体积（0．5±0．010）cm3,而对照组（2．25±0．015）cm3。接受PDT组与对照组比较肿瘤生长速度明显受限。结论体内外实验表明光敏剂HCE6对QBC939系人胆管癌细胞生长具有明显的抑制作用。     

5-氨基-3-乙酰丙酸光动力疗法在肿瘤诊断和治疗中的应用进展

5-氨基-3-乙酰丙酸（5-aminolevulinic acid,5-ALA）是一种内源性的光敏剂,肿瘤细胞和其他恶性细胞可以选择性地吸收外源性5-ALA,使细胞内积聚过量的原卟啉。原卟啉在一定波长的光照射下,发生化学反应,使肿瘤细胞或其他增生活跃的细胞坏死、凋亡,这一过程被称为氨基-3-乙酰丙酸-光动力疗法（aminolevulinic acid-photodynamic therapy,ALA-PDT）。本文对ALA-PDT近年来在肿瘤的诊断和治疗中的应用进展作一综述。     

Changing therapeutic paradigms for exudative age-related macular degeneration: antiangiogenic agents and photodynamic therapy

Age related macular degeneration (AMD) is the leading cause of irreversible visual loss in the United States. Overall, approximately 10 - 20% of patients with AMD exhibit the exudative form, which is responsible for most of the estimated 1.2 m cases of severe visual loss from AMD. Visual loss develops in the exudative form of AMD due to abnormal choroidal neovascular membranes (CNVM) that develop under the retina, leak serous fluid and blood, and ultimately cause a blinding disciform scar in, and under, the retina. Currently, the only well-studied and widely accepted method of treatment is laser photocoagulation of the CNVM. However, only a minority of patients with exudative AMD show well-demarcated ‘classic’ CNVM amenable to laser treatment, and at least half of these patients suffer persistent or recurrent CNVM formation within two years. In addition, since the treatment itself causes a blinding central scotoma when the CNVM is located subfoveally, many clinicians do not treat subfoveal CNVM. With these treatment limitations, there has been a great deal of interest in alternative therapies for AMD, including anti-angiogenic agents and photodynamic therapy. Angiogenesis involves a complex interplay of cellular events involving a cascade of factors that are both inhibitory and stimulatory. Soluble growth factors have been the best-known cell modulating agents in ophthalmology, but there are a multitude of potential sites for inhibition of angiogenesis by pharmacological agents. With regard to photodynamic therapy, a photosensitising dye is injected intravascularly and low power laser light is used to activate the dye within the CNVM to cause vascular occlusion by a photochemical reaction. Closure of the CNVM is achieved without severe collateral damage to the non-vascular tissues as occurs with laser photocoagulation.     

Photosensitisers for the photodynamic therapy of cancer and other diseases

Photodynamic therapy is a relatively recent addition to the clinic, primarily for the treatment of cancer but also for psoriasis, age-related macular degeneration and other diseases. Photodynamic therapy utilises a photosensitiser that targets the disease site to produce a photochemical reaction following delivery of light. The properties of the photosensitiser are critical to the outcome of the technique and numerous classes have been developed in the past decade, including porphyrins and related compounds, chlorins, phthalocyanines, naphthalocyanines, texaphyrins, core-modified porphyrins and various cationic dyes. The potential of this technique is apparent from the extensive number of patents that have been awarded over the past three years.     

Bilateral punctal–canalicular stenosis following photodynamic therapy for choroidal neovascularization

Several medications have been reported to cause punctal–canalicular stenosis, such as mitomycin C, docetaxel, 5-fluorouracil, and isotretinoin. To our knowledge, there have been no cases of verteporfin-associated punctal–canalicular stenosis described in the literature. We hereby present such a case.     

新型给药系统和新技术在光动力疗法中的应用

目的 阐述新型给药系统和制剂新技术在改善光动力疗法（photodynamic therapy,PDT）中的应用研究进展。方法 根据文献,对脂质体、纳米粒、聚合物胶束、微粒表面修饰、微针阵列技术、电学技术、自发光技术、上转换技术等新型给药系统和制剂新技术在PDT中的研究新进展进行阐述。结果 新型给药系统和制剂新技术在较好改善多数光敏剂生理条件下呈疏水性、易聚集及对病变组织选择性不高方面具有独特优势,值得进一步研究。结论 新型给药系统和制剂新技术的开发,有希望将光敏剂传递到人体较深部位并浓集于靶组织,具有广阔的应用前景。     

Effect of Oil-in-Water Emulsions on 5-Aminolevulinic Acid Uptake and Metabolism to PpIX in Cultured MCF-7 Cells

No HeadingPurpose. To identify the optimal vehicle for fast and efficient cellular production of the photosensitizer, protoporphyrin IX (PpIX), upon administration of 5-aminolevulinic acid (ALA).Methods. ALA in various oil/water o/w emulsions was applied to the human mammary epithelial cell line (MCF-7) cultured in microplates. Upon incubation for 1–4 h, the accumulated amount of PpIX was determined by fluorescence spectroscopy. Variables such as the pH and concentration of the emulsions, the temperature and duration of incubation were examined along with the importance of ALA concentration and the presence of endocytosis inhibitors.Results. An increase in the amount of produced PpIX was observed with an increase in extracellular pH, incubation temperature, and ALA concentration. A saturable mechanism of PpIX accumulation was evident, mainly as a result of the uptake mechanism for ALA. Some of the o/w emulsions increased the amount of intracellular PpIX, and the results indicated that this was not due to an increased k_m of the extracellular ALA to intracellular PpIX conversion, but to the increased endocytotic uptake in the presence of the emulsions. In general, the increase in PpIX in the presence of emulsions relative to the control was more pronounced after 1 h as compared to after 2–4 h.Conclusions. The formation of PpIX in MCF-7 cells exposed to ALA is improved by the presence of certain o/w emulsions, which could be explained by endocytosis.     

光动力疗法治疗年龄相关性黄斑变性的临床疗效与基因多态性关联研究现状

年龄相关性黄斑变性(AMD)是黄斑的异质性疾病,在西方国家已成为老年人致盲及视力下降的首要因素。光动力疗法(PDT)选择性较高,对周围组织损伤小,是AMD的主要治疗方法之一。但应用PDT治疗的疗效有显著的个体间差异,这种差异与遗传因素有关。本文将对PDT疗效相关的药物基因组学研究进行综述,以期为通过基因检测指导PDT个体化治疗提供参考。     

5-氨基酮戊酸对人舌麟癌Tea8113细胞株体外光动力杀伤作用的基础研究

目的初步研究体外5-氨基酮戊酸介导的光动力疗法对人舌鳞癌Tea8113细胞的杀伤效应。方法体外培养Tca8113细胞,以5-氨基酮戊酸为光敏剂,半导体激光治疗仪给予光动力疗法,采用MTr法检测光敏剂不同孵育时间、不同光敏剂浓度对Tea8113细胞抑制率的影响。结果5-AIA—PDT作用后,Tea8113细胞生长受到抑制,孵育时间和浓度效应关系显著（P〈0．05）。药物最佳作用浓度为1mmoL／l,最佳孵育时间为6h。结论5-氨基酮戊酸一光动力疗法能有效杀伤Tea8113细胞,光敏剂孵育时间、光敏剂浓度是影响疗效的重要因素。     

Alginate-based aerogels as wound dressings for efficient bacterial capture and enhanced antibacterial photodynamic therapy

The development of novel wound dressings, such as aerogels, with rapid hemostasis and bactericidal capacities for pre-hospital care is necessary. To prevent the occurrence of bacterial resistance, antibacterial photodynamic therapy (aPDT) with broad-spectrum antibacterial ability and negligible bacterial resistance has been intensively studied. However, photosensitizers often suffer from poor water solubility, short singlet oxygen (¹O₂) half-life and restricted ¹O₂ diffusion distance. Herein, sodium alginate was covalently modified by photosensitizers and phenylboronic acid, and cross-linked by Ca(II) ions to generate SA@TPAPP@PBA aerogel after lyophilization as an antibacterial photodynamic wound dressing. Afterwards, its photodynamic and bacterial capture activities were intensively evaluated. Furthermore, its hemostasis and bactericidal efficiency against Staphylococcus aureus were assessed via in vitro and in vivo assays. First, chemical immobilization of photosensitizers led to an enhancement of its solubility. Moreover, it showed an excellent hemostasis capacity. Due to the formation of reversible covalent bonds between phenylboronic acid and diol groups on bacterial cell surface, the aerogel could capture S. aureus tightly and dramatically enhance aPDT. To sum up, the prepared aerogel illustrated excellent hemostasis capacity and antibacterial ability against S. aureus. Therefore, they have great potential to be utilized as wound dressing in clinical trials.