Optical imaging guided resection and photodynamic therapy of glioma with targeted photoactivable agents

项目说明 胶质母细胞瘤(GBM)是一种毁灭性的疾病，存活率很低(2-5%)。复发性 导致大部分死亡的疾病是局部的(95%)，距离切除床几毫米。完整的外科手术 由于基底膜细胞侵袭性生长到周围的正常脑组织，切除手术很少可行。 大块肿瘤。此外，这些浸润性细胞具有高度的迁移性，并表现出生化变化，从而使 上升到治疗抗药性。利用荧光技术显著延长生存时间(~28%) 引导切除(FGR)后光动力疗法(PDT，一种基于光化学的疗法)和OUR 其他人致力于机械设计的基于光动力疗法的联合疗法来治疗耐药癌症 细胞，我们建议在浸润性的GBM细胞中特异性靶向表皮生长因子受体(EGFR)。 超越手术切除边缘的一种方法，我们称之为靶向光激活多智能体 采用图像引导剂量学的脂质体(TPMALs)。TPMAILs将整合FDA批准的PDT试剂 (苯并卟啉衍生物，BPD)、成像造影剂(IRDye800)和多RTK抑制剂。EGFR是 在70%的浸润性耐药基底膜中均有表达。BPD和近红外示踪剂IRDye®800CW 结合到TPMAL膜中能够实现多波长荧光和光声成像 TPMAL为残留、不能切除的疾病提供PDT光剂量学设计和在线记者 治疗反应监测。拟议的研究提供了一个令人信服的机会 哈桑博士在美国的实验室(光动力疗法和癌症纳米药物输送系统)和图尔钦博士的实验室的专业知识 (生物光子学和多模式荧光和光声成像系统)在俄罗斯解决 上面提到的挑战是利用纳米技术和光学成像方面的进步 组。生物学(体外和体内)和纳米表征实验将在哈山进行 实验室和技术方面(成像系统开发、模拟和数据/图像处理) 在图尔钦实验室完成。哈桑博士高度互补的研究实验室之间的合作 而图尔钦将建立一个基于纳米技术的图像引导定制治疗平台，能够 快速评估联合治疗的疗效，并具有较高的临床转译潜力 视网膜母细胞瘤的PDT和影像引导下切除。两个团队都期待着在项目之外继续努力，因为 从科学上讲，这里开发的技术具有巨大的潜力，可以透明地适应其他 癌症类型。

Project Description Glioblastoma (GBM) is a devastating disease with dismal statistics for survival (2–5% overall). Recurrent disease responsible for most mortality is local (95%) few mm from the resection bed. Complete surgical resection is rarely feasible due to the invasive growth of GBM cells into normal brain tissue surrounding the bulk tumor. Moreover, these infiltrative cells are highly migratory and exhibit biochemical alterations that give rise to treatment resistance. Leveraging the significant increase (~28%) in survival time using fluorescence guided resection (FGR) followed by photodynamic therapy (PDT, a photochemistry based therapy) and our and others works on mechanistically designed PDT-based combination therapies to treat drug-resistant cancer cells, we propose to specifically target the epidermal growth factor receptor (EGFR) in infiltrative GBM cells beyond the margins of surgical resection in an approach we term as Targeted Photoactivatable Multi-Agent Liposomes (TPMALs) with image-guided dosimetry. The TPMAILs will integrate an FDA-approved PDT agent (benzoporphyrin derivative, BPD), an imaging contrast agent (IRDye800) and a multi-RTK inhibitor. EGFR is expressed in 70% of infiltrative drug resistant GBMs. BPD and a near-infrared tracer IRDye®800CW incorporated into the TPMAL membrane enable multi-wavelength fluorescence and photoacoustic imaging as online reporters of TPMAL delivery to residual, unresectable disease for PDT light dosimetry design and treatment response monitoring. The proposed study provides a compelling opportunity to bring together expertise of Dr. Hasan's lab (PDT and nano-drug delivery systems for cancer) in USA and Dr. Turchin's lab (Biophotonics and multi-modality fluorescence and photoacoustic imaging systems) in Russia to address the challenges mentioned above by leveraging advances in nanotechnology and optical imaging from both the groups. The biological (in vitro and in vivo) and nano-characterization experiments will be performed at Hasan lab and the technical aspects (imaging system development, simulations and the data/image processing) performed at Turchin lab. The collaboration between the highly complementary research labs of Drs. Hasan and Turchin will establish a nanotechnology based image-guided customized treatment platform capable of rapidly evaluating combination therapy efficacy and has high potential for clinical translation given the success of PDT and image-guided resection in GBM. Both teams look forward to continue efforts beyond the project as scientifically the techniques developed here have tremendous potential for transparent adaption to other cancer types.