Nanoscale Metal-organic Frameworks for Light Triggered and X-ray Induced Photodynamic Therapy of Head and Neck Cancers

用于光触发和 X 射线诱导光动力治疗头颈癌的纳米级金属有机框架

基本信息

批准号：
8959832
负责人：
Wenbin Lin
金额：
$ 57.58万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-25 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8959832
关键词：
Accounting Address Adverse effects Aftercare Blood Circulation Time Cell Line Cells Characteristics Chemicals Clinical Disease Dose Energy Transfer Evaluation Generations Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Health In Vitro Injection of therapeutic agent Lanthanoid Series Elements Lead Light Lighting Malignant Epithelial Cell Malignant Neoplasms Metals Modality Normal tissue morphology Operative Surgical Procedures PUVA Photochemotherapy Particle Size Patients Penetration Photophobia Photosensitizing Agents Porosity Porphyrins Procedures Radiation Radiation therapy Reactive Oxygen Species Resistance Roentgen Rays Structure Surface Technology Therapeutic Tissues Toxic effect Translations Treatment Efficacy Xenograft procedure absorption animal imaging antitumor effect base cancer cell cancer recurrence cancer therapy cancer type chemotherapy clinical application image guided improved in vivo irradiation killings mortality mouse model nanoparticle nanoscale neoplastic cell novel particle scale up subcutaneous treatment strategy tumor

项目摘要

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Clinically used combination of radiation therapy and chemotherapy is the most common curative treatments for HNSCC, but causes many undesirable side effects and will incur resistance. Photodynamic therapy (PDT) is an effective anticancer procedure but its clinical application is limited due to the extreme light sensitivity o patients before and after treatment, the suboptimal reactive oxygen species generation efficiency, and the shallow tissue penetration of light (< 1 cm). Nanoparticle photosensitizers (PSs) can selectively accumulate in tumors and thus alleviate the light sensitivity issue. NIR triggered PDT and X-ray induced PDT (X-PDT) have the ability to combine the strengths of the improved tissue penetration depth of NIR and X-ray and the advantages of PDT for deep tumor treatment. We herein propose to develop an entirely new class of nanoparticle PSs based on nanoscale metal-organic frameworks (NMOFs) that have the ideal characteristics of tunable chemical compositions, crystalline structures, extremely high porosity, short-term stability, and long-term bio- degradability to enable NIR triggered PDT for superficial tumors and X-PDT for deep tumors. This project addresses the unmet needs in developing highly efficient and safe nanoparticle PSs that can have much broader clinical applications for cancer by NIR-triggered PDT or X-PDT. We propose the following aims: AIM 1: Synthesis and characterization of NMOFs for NIR triggered and X-PDT. We will optimize NMOF structures, particle sizes, and surface characteristics to achieve NIR-triggered PDT and X-PDT with improved efficiency. Efforts will also be made for scaled-up NMOF synthesis and surface functionalization to achieve long blood circulation times. AIM 2: Evaluation of NIR triggered PDT efficacy for HNSCC. The NIR-PDT efficacy of NMOFs will be evaluated against multiple HNSCC cell lines in vitro. We will investigate the in vivo toxicity and efficacy of one most potent NMOF identified at cellular level against HNSCC subcutaneous xenograft and orthotopic mouse models. AIM 3: Evaluation of X-ray induced PDT efficacy for HNSCC. The X-PDT efficacy of NMOFs will be investigated against HNSCC cells in vitro. For the in vivo studies, we will first evaluate the toxicity of the NMOFs and the X-PDT treatment alone. The in vivo anticancer efficacy will be carried out on both subcutaneous and orthotopic HNSCC mouse models with the two most potent NMOFs identified at cellular level. We will also apply state-of-the-art small-animal image-guided X-Ray delivery technology to enable image-guided X-PDT, toward translation to clinical radiotherapy

描述（由应用提供）：头部和颈部鳞状细胞癌（HNSCC）是全球第六大癌症。放射疗法和化学疗法的临床结合是HNSCC的最常见治疗疗法，但会引起许多不良的副作用，并会产生耐药性。光动力疗法（PDT）是一种有效的抗癌手术，但由于治疗前后，其临床应用受到限制。纳米颗粒光传感器（PSS）可以选择性地积聚在肿瘤中，从而减轻光灵敏度问题。 NIR触发的PDT和X射线诱导的PDT（X-PDT）具有结合NIR和X射线的组织穿透深度的强度以及PDT在深肿瘤治疗方面的优势。我们在这里提出的建议是，基于纳米级金属有机框架（NMOFS）开发全新的纳米颗粒PSS，它们具有可调化学成分的理想特征，结晶结构，极高的孔隙度，短期稳定性，长期的生物稳定性和长期的生物依赖性以及为NIR触发的PDT提供表面和X-pdt的nir触发PDT。该项目解决了开发高效且安全的纳米颗粒PSS的未满足需求，这些PSS可以通过NIR触发的PDT或X-PDT在癌症上具有更广泛的临床应用。我们提出以下目的：目标1：NMOF的NMOF触发和X-PDT的合成和表征。我们将优化NMOF结构，粒径和表面特性，以提高效率，以实现NIR触发的PDT和X-PDT。还将努力用于扩大NMOF合成和表面功能化，以达到长血液循环时间。 AIM 2：评估NIR触发HNSCC的PDT效率。 NMOF的NIR-PDT效率将在体外对多个HNSCC细胞系进行评估。我们将研究一个在细胞水平上针对HNSCC皮下异种移植和原位小鼠模型在细胞水平上鉴定出的最潜在NMOF的体内毒性和效率。 AIM 3：评估HNSCC的X射线诱导PDT功效。 NMOF的X-PDT效率将在体外对HNSCC细胞进行研究。对于体内研究，我们将首先评估NMOF和X-PDT治疗的毒性。体内抗癌效率将在皮下和原位HNSCC小鼠模型上进行，并在细胞水平上鉴定出两个最潜在的NMOF。我们还将应用最先进的小动物图像引导的X射线输送技术来启用图像引导的X-PDT，以转化为临床放射疗法