光动力联合抗生素治疗大鼠创伤感染北大核心CSCD

探讨了新型卟啉类光敏剂PA1介导的光动力抗菌(PACT)联合抗生素治疗重度创伤感染大鼠的效果并简要探讨其机制。健康雄性Wistar大白鼠24只(清洁级)作为实验对象,建立大面积创伤感染模型,随机分成模型对照组、PACT治疗组、抗生素治疗组、PACT联合抗生素治疗组,每组6只,共治疗8d。检测不同时间点各组创面下的菌落数和创面愈合率,并采用酶联免疫吸附测定(ELISA)方法检测创面周边组织碱性成纤维因子(bFGF)、肿瘤坏死因子α(TNF-α)和白介素6(IL-6)的表达。结果表明PACT联合抗生素治疗与模型对照组相比能显著减轻大鼠创伤组织的炎症,减少创面组织中细菌的数量,加快创面愈合速率,缩短创面愈合时间;同时还能提高创面组织中bFGF的含量,抑制组织中炎症相关因子TNF-α和IL-6的表达,其效果优于单用PACT的治疗组和单用抗生素的治疗组。结果表明PACT联合抗生素可以治疗大面积创伤感染。     

光动力疗法中最佳光动力治疗剂量的研究

为了研究光动力过程中光剂量和光敏剂剂量对光动力损伤效果的影响,基于肿瘤组织中光动力损伤剂量的数学模型以及光动力损伤剂量与组织中光剂量、光敏剂剂量、氧浓度之间的函数关系,用数学方法模拟研究了给定模型组织中光及光敏剂的有效吸收剂量与氧浓度之间的关系,并用ALA-PDT实验研究了k562细胞悬浮液中不同药物剂量对光动力损伤效果的影响.研究发现,光动力过程中光剂量与光敏剂浓度存在一个最佳治疗剂量,其大小和组织中氧浓度有关,组织中越缺氧,最佳光动力剂量越小,光动力过程对组织的损伤越小,通过实验发现k562细胞悬浮液中最佳剂量为20×0.25(J/cm2·mmol/L),此时光动力损伤效果最明显.研究结果表明了PDT对肿瘤组织具有选择性光动力损伤的特点,并为PDT在临床上的广泛应用提供了理论支持.     

中药光敏剂介导的光动力疗法

光动力疗法是现代肿瘤治疗中的一种新方法。光敏剂的选择是肿瘤光动力治疗中的关键和核心问题。近年来研究发现 ,某些中草药如姜黄素、黄柏、补骨脂素等具有一定的光敏活性作用。基于中草药提取物中研制的高效、低毒的新型理想光敏剂介导的光动力治疗正倍受人们的普遍青睐     

新型光敏剂四间羟基苯基二氢卟吩介导光动力治疗的研究进展

光动力疗法(PDT)是一种有前途的治疗肿瘤的新方法,而新型光敏剂m-THPC的低毒性、高效率使其成为有潜力的光动力药物,因此m-THPC-PDT在治疗肿瘤方面具有较高的研究价值。     

蒙特卡罗方法研究光动力疗法选择性光损伤

为了研究光动力疗法选择性光损伤,采用蒙特卡罗方法,建立了组织中光动力剂量数学模型。得到光动力剂量随组织厚度增加呈指数衰减的结果。光动力损伤是阈值过程,对肿瘤组织造成深层光动力损伤时,更多正常组织受到损伤。光斑半径对对肿瘤组织损伤深度有明显影响。结果表明,适量光敏剂能引起浅薄全面的肿瘤组织光动力损伤,深层光动力损伤伴随正常组织损伤。     

光动力增效研究进展

光动力疗法作为一种新兴的非侵入性治疗方法,由于其高度的选择性、良好的美容效果、可重复性以及低副作用,受到了越来越多的关注.虽然光动力疗法研究已经取得了很多进展,但是由于光敏剂的靶向问题、光的穿透性缺陷、肿瘤组织内缺氧环境等因素局限了光动力疗法的效果.近年来许多研究者对突破光动力的限制,增强其功效进行了研究.本综述主要从...     

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...     

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。     

Inverse Opal Photonic Hydrogels for Blue-Edge Slow Photon-Enhanced Photodynamic Antibacterial Therapy

Photodynamic therapy is promising for combating bacteria by reactive oxygen species. However, the therapeutic efficiency of photodynamic antibacterial therapy (PDAT) is largely hindered by limited photon absorption and the low quantum yield of photosensitizers. Herein, a novel light-harvesting platform is designed by decorating photosensitizer chlorine e6 (Ce6) into an inverse opal photonic hydrogel (Ce6/IOPG) framework for efficient light utilization to enhance PDAT. It is shown that the generating efficiency of singlet oxygen (¹O₂) can be tuned by the relative positions of the photonic bandgap (PBG) of IOPG and the absorption band of Ce6. The coupling of the slow photon effect with the efficient dispersion of Ce6 allows for a maximum generation of ¹O₂ of approximately 69.5-fold and markedly enhances PDAT activity upon low light irradiation when the blue edge of PBG overlaps with the absorption band of Ce6. Particularly, slow photons at the blue edge show advantages in improving ¹O₂ generation compared to those at the red edge. The variation in ¹O₂ generation by altering the incident angle of light provides direct evidence for the slow photon effect in Ce6/IOPG. This work provides insights into blue-edge slow photons in photodynamic enhancement and offers an advisable design principle for efficient antibacterial therapy.     

Biofilm-Sensitive Photodynamic Nanoparticles for Enhanced Penetration and Antibacterial Efficiency

Efficient antimicrobials are urgently needed for the treatment of bacterial biofilms due to their resistance to traditional drugs. Photodynamic therapy (PDT) is a new strategy that has been used to combat bacteria and biofilms. Cationic photosensitizers, particularly cationic photodynamic nanoagents, are usually chosen to enhance photodynamic antimicrobial activity. However, positively charged nanoparticles (NPs) are beneficial to cellular internalization, which causes increased cell cytotoxicity. Herein, a pH-sensitive photodynamic nanosystem is designed. Rose Bengal (RB) polydopamine (PDA) NPs are decorated in a layer-by-layer fashion with polymyxin B (PMB) and gluconic acid (GA) to generate functionally adaptive NPs (RB@PMB@GA NPs). RB@PMB@GA NPs remain negative at physiological pH and exhibit good biocompatibility. When RB@PMB@GA NPs are exposed to an acidic infectious environment, the surface charge of the NPs is, in turn, positively charged as a result of pH-sensitive electrostatic interactions. This surface charge conversion allows the RB@PMB@GA to effectively bind to the surfaces of bacteria and enhance photoinactivation efficiency against gram-negative bacteria. Most importantly, RB@PMB@GA NPs exhibit good biofilm penetration and eradication under acidic conditions. Furthermore, RB@PMB@GA NPs efficiently eliminate biofilm infections in vivo. This study provides a promising strategy for safely treating biofilm-associated infections in vivo.     

A Dual‐Functional Photosensitizer for Ultraefficient Photodynamic Therapy and Synchronous Anticancer Efficacy Monitoring

A dual‐functional photosensitizer that demonstrates exceptional photodynamic therapy (PDT) efficacy while simultaneously self‐monitoring the therapeutic response in real time is reported here. Possessing an ultrahigh ¹O₂ quantum yield of 98.6% in water, the photosensitizer TPCI can efficiently induce cell death in a series of carcinoma cells (IC₅₀ values less than 300 × 10^?9 m ) upon irradiation with an extremely low fluence (460 nm, 4 mW cm^?2 for 10 min). In addition, TPCI can self‐monitor cell death in real time. It is weakly fluorescent in living cells before irradiation and lights up the nuclei concomitantly with cell death during PDT treatment by binding with chromatin to activate its aggregation‐induced emission, attributed to its strong binding affinity with DNA. In vivo studies using mouse models bearing H22 and B16F10 tumor cells validate the ultraefficient PDT efficacy of TPCI as well as the precise real‐time noninvasive readout of the tumor response from the beginning of cancer treatment. The dual‐functional TPCI serves as an excellent candidate for single‐agent photodynamic theranostics, and this work represents a new paradigm for the development of molecules with multiple intrinsic functions for future self‐reporting medical applications.     

鲜红斑痣光动力治疗数学模型及临床验证

为了研究光动力治疗(PDT)中各个因素作用的规律,帮助临床采取有效的治疗方案,针对鲜红斑痣(PWS)组织特性,将光动力治疗中组织光分布、单线态氧产生、光敏剂漂白过程和光敏剂扩散过程结合起来,建立适合于光动力治疗鲜红斑痣病变的系统模型。利用建立的模型,对临床中出现的第二光斑治疗效果差的问题进行仿真研究,发现影响其治疗效果的因素,并通过仿真实验提出改进其治疗效果的新方案。通过临床实验,证明了新方案的有效性和模型的有效性。研究结果说明,针对特定的病例条件建立仿真模型,通过仿真实验可以为临床和理论研究提供一种有效的分析方法。     

光动力法制备抗小鼠H22肝癌的肿瘤疫苗

研究了光动力疗法(PDT)制备的抗小鼠H22肝癌肿瘤疫苗的抗瘤效应.将昆明鼠60只,随机分为2组,每组30只.实验组取6~12周龄的昆明鼠背部皮下接种光动力疗法产生的疫苗,每3天注射一次,每次注射50μL(相当于3×105个细胞),连续两周.隔一周于第22天注射H22肿瘤细胞悬液0.1 mL(1×106个细胞);对照组:每周每次注射50μL生理盐水,连续两周.隔一周于第22天注射H22肿瘤细胞悬液0.1 mL(1×106个细胞).比较两组的抑瘤率、生存率以及两组之间免疫学的相关指标.结果表明,实验组小鼠具有显著的抑瘤效果,抑瘤率、生存率较对照组有显著提高.实验组肿瘤抑瘤率最高可达60%且长期有效,100天生存率达56%.说明光动力疗法产生的抗小鼠H22肝癌疫苗可以有效地抑制肿瘤生长,提高荷瘤小鼠的生存率,具有明显的抗瘤效应.该方法可能成为一种辅助性治疗肿瘤的手段而应用于临床.     

Activatable Photosensitizers: Agents for Selective Photodynamic Therapy

Recent developments in the design of bifunctional and activatable photosensitizers rejuvenate the aging field of photodynamic sensitization and photodynamic therapy. While systematic studies have uncovered new dyes that can serve as potential photosensitizers, the most promising results have come from studies aimed at gaining precise control over the location and rate of cytotoxic singlet oxygen generation. As a consequence, higher selectivities and efficiencies in photodynamic treatment protocols are now within reach. This feature article highlights the variety of approaches that have been pursued to improve photodynamic therapy and to transform simple photosensitizers into smarter theranostic agents.     

Recent Advances in Nanomaterial-Based Nanoplatforms for Chemodynamic Cancer Therapy

Triggered by the endogenous chemical energy in the tumor microenvironment (TME), chemodynamic therapy (CDT) as an emerging non-exogenous stimulant therapeutic modality has received increasing attention in recent years. The chemodynamic agents can convert internal hydrogen peroxide (H₂O₂) into the lethal reactive oxygen species (ROS) hydroxyl radicals (^•OH) for oncotherapy. Compared with other therapeutic modalities, CDT possesses many notable advantages, such as tumor-specific, highly selective, fewer systemic side effects, and no need for external stimulation. Nevertheless, mild acid pH, low H₂O₂ content, and overexpressed reducing substance in TME severely suppressed the CDT efficiency. With the rapid development of nanotechnology, some kinds of nanomaterials have been utilized with improved CDT efficiency. In particular, the excellent photo-, ultrasound-, magnetic-, and other stimuli-response properties of nanomaterials make it possible for combination cancer therapy of CDT with other therapeutic modalities, and it has shown superior anti-cancer activity than monotherapies. Therefore, it is necessary to summarize the application of nanomaterial-based chemodynamic cancer therapy. In this review, the various nanomaterials-based nanoplatforms for CDT and its combinational therapies are summarized and discussed, aiming to provide inspiration for the design of better-quality agents to promote the CDT development and lay the foundation for its future conversion to clinical applications.     

利用激光散斑成像监测光动力治疗的血管损伤效应

激光散斑衬比成像(LSCI)技术作为一种高时空分辨的血流流速分布监测技术，无需扫描即可实时地全场记录微循环血流的时空变化特性。鸡胚尿囊膜(CAM)是用于在体研究光动力治疗(PDT)血管损伤效应的理想动物模型。以发育10天鸡胚尿囊膜为模型，使用光敏剂——焦脱镁叶绿酸(pyropheophorbide acid，pyro-acid)，激光照射波长为656．5nm，光照射功率为40mW／cm^2，研究了肿瘤周围血管在激光照射下的血管管径变化和血流速度分布变化。研究表明，通过对血管管径和血流速度的监测，激光散斑衬比成像技术可以用于评估光动力治疗过程中的肿瘤周围血管损伤效应。     

The AIE-Active Dual-Cationic Molecular Engineering: Synergistic Effect of Dark Toxicity and Phototoxicity for Anticancer Therapy

The development of anticancer therapy is significant to human health but remains a huge challenge. Photodynamic therapy (PDT), inducing the synergistic mitochondrial dysfunction in cancer cells is a promising approach but suffer from the low efficiency in hypoxic microenvironment and deep-seated tumors. Herein, to improve the outcomes of PDT for cancer treatment, a series of red fluorophores consisting of dual-cationic triphenylphosphonium-alkylated pyridinium and (substituted) triphenylamine are prepared as organelle-targeting antitumor photosensitizers (PSs) with aggregation-induced emission characteristics. These PSs can selectively accumulate at the mitochondria or lysosomes of cancer cells with both dark- and photo-cytotoxicity, making them possess excellent killing effect on cancer cells and efficient inhibition of tumor growth in living mice. This study brings about new insight into the development of powerful cancer treatment.     

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。