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首页> 外文会议>Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XV; Progress in Biomedical Optics and Imaging; vol.7 no.25 >Synthesis, Characterization and Preclinical Studies of Two-Photon-activated Targeted PDT Therapeutic Triads
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Synthesis, Characterization and Preclinical Studies of Two-Photon-activated Targeted PDT Therapeutic Triads

机译：二光子激活的靶向PDT治疗三联征的合成，表征和临床前研究

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Photodynamic therapy (PDT) continues to evolve into a mature clinical treatment of a variety of cancer types as well as age-related macular degeneration of the eye. However, there are still aspects of PDT that need to be improved in order for greater clinical acceptance. While a number of new PDT photo-sensitizers, sometimes referred to as second- or third-generation therapeutic agents, are currently under clinical investigation, the direct treatment through the skin of subcutaneous tumors deeper than 5 mm remains problematic. Currently approved PDT porphyrin photo-sensitizers, as well as several modified porphyrins (e.g. chlorins, bacteriochlorins, etc.) that are under clinical investigation can be activated at 630-730 nm, but none above 800 nm. It would be highly desirable if new PDT paradigms could be developed that would allow photo-activation deep in the tissue transparency window in the Near-infrared (NIR) above 800 nm to reduce scattering and absorption phenomena that reduce deep tissue PDT efficacy. Rasiris and MPA Technologies have developed new porphyrins that have greatly enhanced two-photon absorption (TPA) cross-sections and can be activated deep in the NIR (ca. 780-850 nm). These porphyrins can be incorporated into a therapeutic triad that also employs an small molecule targeting agent that directs the triad to over-expressed tumor receptor sites, and a NIR one-photon imaging agent that allows tracking the delivery of the triad to the tumor site, as well as clearance of excess triad from healthy tissue prior to the start of PDT treatment We are currently using these new triads in efficacy studies with a breast cancer cell line mat has been transfected with luciferase genes that allow implanted tumor growth and post-PDT treatment efficacy studies in SCID mouse models by following the rise and decay of the bioluminescence signal. We have also designed highly absorbing and scattering collagen breast cancer phantoms in which we have demonstrated dramatic cell kill to a depth of at least 4 cm. We have also demonstrated that at the wavelength and laser fluences used in the treatment of implanted tumors in the mouse mammary fat pads, there is little, if any, damage to the skin or internal mouse organs. In addition, we have also demonstrated that the implanted tumors can be treated to a depth of more than 1 cm by direct radiation through the dorsal side of the mouse.
机译：光动力疗法（PDT）继续发展成为各种癌症类型以及与年龄相关的黄斑变性的成熟临床疗法。但是，PDT的某些方面仍需要改进，以提高临床接受度。尽管目前正在临床研究许多新的PDT光敏剂，有时也称为第二代或第三代治疗剂，但通过皮肤直接治疗深度超过5毫米的皮下肿瘤仍然存在问题。目前批准用于临床研究的PDT卟啉光敏剂以及几种经过修饰的卟啉（例如二氢卟酚，细菌绿素等）可以在630-730 nm激活，但在800 nm以上不会激活。如果可以开发出新的PDT范式，这将是非常可取的，它将允许在高于800 nm的近红外（NIR）中的组织透明窗口中进行光激活，以减少散射和吸收现象，从而降低深层组织PDT的功效。 Rasiris和MPA Technologies开发了新的卟啉，这些卟啉极大地增强了两光子吸收（TPA）截面，并且可以在NIR的深处（约780-850 nm）被激活。可以将这些卟啉掺入治疗性三联症，该疗法还采用了将三联症引导至过度表达的肿瘤受体位点的小分子靶向剂，以及允许追踪三联症向肿瘤部位递送的NIR单光子成像剂，以及在开始PDT治疗之前从健康组织中清除多余的三联征我们目前正在将这些新的三联征用于乳腺癌细胞系垫的功效研究中，该垫已被荧光素酶基因转染，从而允许植入的肿瘤生长和PDT治疗后通过跟踪生物发光信号的上升和下降，在SCID小鼠模型中进行功效研究。我们还设计了高度吸收和散射的胶原蛋白乳腺癌幻象，其中我们证明了至少4厘米深度的细胞杀伤力。我们还证明，在用于治疗小鼠乳腺脂肪垫中植入的肿瘤的波长和激光注量下，对皮肤或小鼠内部器官的损害很小（如果有的话）。另外，我们还证明了通过直接照射通过小鼠背侧可以将植入的肿瘤治疗到1 cm以上的深度。

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