聚合物纳米粒在肿瘤光动力治疗中的研究进展

光动力治疗创伤小,在恶性肿瘤治疗方面的应用已经得到了临床认可。治疗过程中需要给予光敏剂,在光照下产生分子氧对肿瘤细胞产生杀伤作用。但是,大多数光敏剂缺乏对肿瘤细胞的特异性,其在肿瘤中的富集主要与细胞高代谢有关,并且在水相媒介中溶解度比较差。纳米技术应用于光动力治疗提供了一种有效地体内运输光敏剂的方式。目前,聚合物纳米粒与光动力药物传递的研究越来越多,光敏剂通过纳米粒的运输为弥补光动力治疗的不足提供了可能,这是因为纳米载体可以将治疗浓度的光敏剂运送到肿瘤细胞而不造成非靶向组织的副损伤。本文将介绍对肿瘤光动力治疗中具有特异性的聚合物纳米粒的种类及在临床中的应用情况,为肿瘤靶向治疗提供新思路。     

结直肠癌的光动力治疗进展

结直肠癌是消化系统最常见的恶性肿瘤之一,且发病率逐年上升,但其治疗往往仅限于手术、放疗、化疗等传统方法。近年来,光动力疗法在结直肠癌治疗中取得了满意效果。本文对近年来国内外应用光动力疗法治疗结直肠癌的文献进行综述,系统阐述这一治疗方法的起源与发展、作用原理及机制、光敏剂与光源的选择、临床效果、不良反应、制约发展因素及可能解决办法。希望通过本文,为临床医师治疗结直肠癌提供一种新的治疗手段。     

光动力治疗与抗肿瘤免疫

光动力治疗是通过特定波长的光激发光敏剂产生活性氧反应物实现对微生物和肿瘤细胞的杀伤。由于光动力治疗的疗效确切,副作用小,并易于与其他治疗方式联用,因而已成为临床肿瘤治疗的新手段。近年来,抗肿瘤免疫的基础研究和临床应用获得了重大进展。研究表明,光动力治疗与抗肿瘤免疫治疗的联合应用具有显著的协同抗肿瘤效应。本文综述了光动力治疗研究进展及其在抗肿瘤免疫治疗的应用,讨论了其面临的障碍及发展前景。     

基于病灶图像特征提取的光动力治疗方案

识别和分析病灶区域是光动力治疗的一个重要环节。以鲜红斑痣疾病为例,光动力治疗是利用光、光敏剂和分子氧对病变细胞进行强烈的光动力作用,让活性氧杀死病变细胞,最终达到治疗疾病的目的。传统的治疗方案存在病灶区域无法精确诊断、无法精准治疗和总体治疗成本较高等问题。本研究方案设计了一款用于照射治疗鲜红斑痣的窄光谱LED光源,根据病灶特征计算病灶区域分布与病灶程度,最后根据计算结果制作非均匀透射密度的胶片,用于精准调控治疗光源强度。试验结果显示,图像特征提取技术、设计的光源和胶片能够解决光动力治疗中无法精确诊断、无法精准治疗和治疗光源均匀性等问题,在试验描述的鲜红斑痣治疗方面具有广阔的应用前景。     

光动力疗法联合声动力疗法在抗肿瘤方面的研究进展

光动力疗法是一种使用光敏药物和激光活化治疗肿瘤疾病的方法。用特定波长的光辐照肿瘤部位,能使选择性聚集在肿瘤组织的光敏药物活化,引发光化学反应破坏肿瘤。然而,光动力疗法在临床上的应用却一直存在治疗深度受限的问题。本文分析了光动力疗法在临床应用中的局限性,并指出光动力疗法联合声动力疗法是一种可以克服光动力疗法治疗深度局限性的新型非侵入性治疗方法。     

光动力疗法在真菌感染性疾病中的应用

随着激素、广谱抗生素和免疫抑制剂在临床上的广泛应用,真菌感染的发病率不断上升,加上真菌耐药性日趋严重,使得抗真菌药物治疗面临的挑战越来越大.光动力疗法是一种具有高度选择性的药械联动技术,越来越多的研究表明光动力疗法能有效对抗念珠菌、马拉色菌等真菌性疾病的感染,该文就光动力疗法的特点以及光动力学疗法治疗真菌感染的现状做一综述,旨在让大家对光动力抗真菌治疗有一个全面深入的了解.     

皮肤光老化的光学评价与治疗技术研究进展

皮肤光老化是一个极其复杂的渐进过程,不仅有临床及组织学方面变化,还有生物化学方面变化。无损、非侵入式的皮肤光老化评价技术和组织热损伤定量技术促进了光学治疗技术的发展,有助于优化选择非消融性光治疗参数。评述了基于光学方法的皮肤光老化评价和治疗技术研究进展。     

纳米金提高光敏剂单态氧产率的研究

光动力疗法是效果很好的癌症微创治疗方法,主要依靠光敏性药物(也称为光敏剂)进行癌细胞杀伤。在光动力治疗中,光敏剂单态氧产率是影响光动力效果的关键因素。利用纳米金的光学特性来提高光敏剂的单态氧产率为研制新型光敏剂来改进光动力治疗方法提供了一种新的途径。利用绿光LED灯、红光LED灯、氙灯和635 nm连续激光四种光源对混合有光敏剂原卟啉Ⅸ和纳米金的溶液进行光照。用单态氧检测试剂测定了光照后的单态氧产率。     

5-ALA在胶质瘤光动力治疗应用的进展

胶质瘤作为常见的颅内恶性肿瘤,传统的手术与放疗化疗联合的治疗方法难以取得令人满意的治疗效果。光动力治疗作为治疗恶性肿瘤有效的辅助方法,在胶质瘤治疗中得到广泛应用。5-氨基乙酰丙酸(5-aminolevulinic acid,5-ALA)是在光动力治疗中应用最多的光敏剂前体物质。多年来针对5-氨基乙酰丙酸(5-aminolevulinic acid,5-ALA)在胶质瘤光动力治疗中的研究主要集中在如何增强光动力效应,这也是许多神经外科医生的兴趣所在。本文结合相关文献,对5-ALA在胶质瘤光动力治疗的研究进展及未来在此领域面临的挑战进行了综述。     

光动力疗法抑制内膜增生的研究

内膜增生继发于各种血管损伤后,是当前血管外科领域的焦点这一,光动力治疗技术可有效抑制内膜增生,逐渐引起人们重视,但从实验研究到临床应用有较大差距。本文综述光动力治疗技术抑制膜增生的作用机理,应用方法,疗效及应用中存在的问题。     

Photodynamic treatment with anionic nanoclays containing curcumin on human triple-negative breast cancer cells: Cellular and biochemical studies

Photodynamic treatment is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with activation of a photosensitizer agent at a specific light. Little is known, however, about the phototoxic properties of curcumin, as a natural phenolic compound, against different types of cancers. It is generally accepted that cellular damage occurs during photo treatment. There is a limitation in using of curcumin as a drug due to its low solubility, but nanoparticles such as anionic nanoclays or layered double hydroxide (LDH) could overcome it. The aim of this study was to investigate cellular responses to curcumin-LDH nanoparticles after photodynamic treatment of MDA-MB-231 human breast cancer cells. For this purpose, the MDA-MB-231 human breast cancer cell line treated with curcumin-LDH nanoparticle and then irradiated (photodynamic treatment). After irradiation, lactate dehydrogenase assay, clonogenic cell survival, cell death mechanisms such as autophagy and apoptosis were determined. Cell cycle distribution after photodynamic therapy (PDT) and also intracellular reactive oxygen species (ROS) generation were measured. The result showed that curcumin-LDH–PDT has a cytotoxic and antiprolifrative effect on MDA-MB-231 human breast cancer cells. Curcumin-LDH–PDT induced autophagy, apoptosis, and G0/G1 cell cycle arrest in human breast cancer cell line. Intracellular ROS increased in MDA-MB-231 cancer cell line after treatment with curcumin-LDH along with irradiation. The results suggest that curcumin-LDH nanoparticle could be considered as a novel approach in the photodynamic treatment of breast cancer.     

Photodynamic therapy and some clinical applications in oncology

Photodynamic therapy (PDT), a new treatment modality for localized cancers involving the selective interaction of visible light with photosensitizers, such as hematoporphyrin derivatives (HpD) or dihematoporphyrin ether/ester (DHE) (Photofrin II). Photodynamic therapy of malignant tumors includes biological, photochemical and photophysical processes. These processes involve: (i) absorption of photosensitizing agent; (ii) selective retention of photosensitizer in tumors and (iii) irradiation of sensitized tumor by laser irradiation. This paper provides a review of photosensitizers, photochemistry, subcellular targets, side effects and lasers involved in photodynamic therapy. In addition, gradual increase in knowledge related to in vivo and in vitro mechanisms of action of PDT, as well as some clinical applications of photodynamic therapy are presented.     

Photodynamic cell-kill analysis of breast tumor cells with a tamoxifen-pyropheophorbide conjugate

We hypothesized that estrogen receptor (ER) in hormone-sensitive breast cancer cells could be targeted for selective photodynamic killing of tumor cell with antiestrogen-porphyrin conjugates by combining the over-expression of ER in hormone-sensitive breast cancer cells and tumor-retention property of porphyrin photosensitizers. In this study we describe that a tamoxifen (TAM)-pyropheophorbide conjugate that specifically binds to ER alpha, caused selective cell-kill in MCF-7 breast cancer cells upon light exposure. Therefore, it is a potential candidate for ER-targeted photodynamic therapy of cancers (PDT) of tissues and organs that respond to estrogens/antiestrogens.     

The influence of photodynamic therapy on apoptosis in human melanoma cell line

Melanoma is the most severe of all skin cancers as it may grow rapidly and metastasize. The application of photodynamic therapy (PDT) opens new perspectives in treatment of this cancer. Numerous studies suggest that the exposure of tumor cells to PDT can lead to cell death via two separate processes: apoptosis or necrosis. The aim of this study was to assess in vitro photodynamic therapy which induces apoptosis in the human Beidegr?m Melanoma (BM) cell line, using neutral comet assay. The cells were incubated with Photofrin II (15 microg/ml and 30 microg/ml) 4 h before and 3 h after irradiation for 5 or 10 min with the light intensity of 10 mW/cm2, using a lamp with red filter (632.8 nm). The percentage of apoptotic cells was significantly higher after PDT comparing to control cells. We observed 25% and 70% of apoptotic cells after shorter irradiation and treatment with 15 microg/ml and 30 microg/ml of Ph II, respectively. After longer irradiation, the respective values were 71.9% and 90%. The results suggest that induction of apoptosis is an important determinant of photodynamic sensitivity in the studied cell line and that some types of DNA damage are dependent on photosensitizer concentration and time of irradiation.     

Synthesis and biological evaluation of glucose conjugated phthalocyanine as a second-generation photosensitizer

Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can’t be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-infrared (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles.     

具有自噬抑制作用的卟啉金属有机框架的制备及其光动力癌症治疗的研究*

光动力疗法(PDT)具有微创、可控、低毒、可重复治疗等优点,已成为临床医学中不可缺少的治疗手段。但由于肿瘤细胞的自我保护机制,大大降低了PDT疗效。使用PDT治疗方法的同时实施药理自噬抑制策略,切断因光动力治疗下严重氧化损伤下的保护性自噬。通过油浴加热法合成卟啉金属有机框架PCN-224,并在PCN-224上负载自噬抑制剂硫酸羟氯喹(HCQ),通过扫描电子显微镜(SEM)、粒径测试(DLS)、紫外可见光谱测试等方法检测,结果表明成功地合成了该材料,增强了卟啉光敏剂的水溶性,并且光照后对4T1小鼠乳腺癌细胞毒性明显增强,且装载了HCQ后进一步提高了肿瘤杀伤能力。     

The outcome of 5-ALA-mediated photodynamic treatment in melanoma cells is influenced by vitamin C and heme oxygenase-1

Photodynamic therapy (PDT) is an important clinical approach for cancer treatment. It involves the administration of a photosensitizer, followed by its activation with light and induction of cell death. The underlying mechanism is an increased production of reactive oxygen species (ROS) leading to oxidative stress, which is followed by cell death. However, effectiveness of PDT is limited due to an initiation of endogenous rescue response systems like heme oxygenase-1 (HO-1) in tumor cells. In recent years, consuming of antioxidant supplements has become widespread, but the effect of exogenously applied antioxidants on cancer therapy outcome remains unclear. Thus, this study was aimed to investigate if exogenous antioxidants might decrease ROS-induced cytotoxicity in photodynamic treatment. Lycopene, β-carotene, vitamin C, N-acetylcysteine, trolox, and N-tert-butyl-α-phenylnitrone in different doses were administered to human melanoma cells prior exposure to photodynamic treatment. Supplementation with vitamin C resulted in a significant decrease of the cell death rate, whereas the other tested antioxidants had no effect on cell viability and oxidative stress markers. The simultaneous application of vitamin C with the HO-1 activity inhibitor zinc protoporphyrine IX (ZnPPIX) caused a considerable decrease of photodynamic treatment-induced cytotoxicity compared to ZnPPIX alone. It can be summarized that exogenously applied antioxidants do not have a leading role in the protective response against photodynamic treatment. However, further studies are necessary to investigate more antioxidants and other substances, which might affect the outcome of photodynamic treatment in cancer therapy.     

4-Thiothymidine sensitization of DNA to UVA offers potential for a novel photochemotherapy

Photochemotherapy, in which ultraviolet radiation (UVR: 280-400 nm) or visible light is combined with a photosensitizing drug to produce a therapeutic effect that neither drug or radiation can achieve alone, is a proven therapeutic strategy for a number of non-malignant hyperproliferative skin conditions and various cancers. Examples are psoralen plus UVA (320-400 nm) radiation (PUVA) and photodynamic therapy (PDT). All existing photochemotherapies have drawbacks - for example the association of PUVA with the development of skin cancer, and pain that is often associated with PDT treatment of skin lesions. There is a clear need to develop alternative approaches that involve lower radiation doses and/or improved selectivity for target cells. In this review, we explore the possibility to address this need by exploiting thionucleoside-mediated DNA photosensitisation to low, non toxic doses of UVA radiation.     

Low‐dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization

Photodynamic therapy (PDT) is an effective clinical treatment for a number of different cancers. PDT can induce hypoxia and inflammation, pro‐angiogenic side effects, which may counteract its angio‐occlusive mechanism. The combination of PDT with anti‐angiogenic drugs offers a possibility for improved anti‐tumour outcome. We used two tumour models to test the effects of the clinically approved angiostatic tyrosine kinase inhibitors sunitinib, sorafenib and axitinib in combination with PDT, and compared these results with the effects of bevacizumab, the anti‐VEGF antibody, for the improvement of PDT. Best results were obtained from the combination of PDT and low‐dose axitinib or sorafenib. Molecular analysis by PCR revealed that PDT in combination with axitinib suppressed VEGFR‐2 expression in tumour vasculature. Treatment with bevacizumab, although effective as monotherapy, did not improve PDT outcome. In order to test for tumour vessel normalization effects, axitinib was also applied prior to PDT. The absence of improved PDT outcome in these experiments, as well as the lack of increased oxygenation in axitinib‐treated tumours, suggests that vascular normalization did not occur. The current data imply that there is a future for certain anti‐angiogenic agents to further improve the efficacy of photodynamic anti‐cancer therapy.     

Evidence for the involvement of singlet oxygen in the photodestruction by chloroaluminum phthalocyanine tetrasulfonate

In recent years, choloroaluminum phthalocyanine tetrasulfonate (A1PCTS) has been shown to be a promising photosensitizer for the photodynamic therapy (PDT) of cancer. Although its mechanism of photodynamic action is not well defined, A1PCTS is going to be under clinical trials of PDT. In this study, in vitro addition of A1PCTS to a suspension of rat epidermal microsomes followed by irradiation with red light (approximately 675 nm) resulted in significant destruction of cytochrome P-450 and associated monooxygenase activities. The photodestructive effect was dependent on both the dose of A1PCTS and the duration of light exposure. Studies using various quenchers of reactive oxygen species showed that only scavengers of singlet oxygen such as histidine, 2,5-dimethylfuran, beta-carotene and sodium azide afforded substantial protection against photodestruction. Our data indicate the direct involvement of singlet oxygen in the A1PCTS-mediated photodestructive process.