Brachytherapy in situ dose-painting administered via gold-nanoparticle eluters

描述(由申请人提供)：应聘者表现出了成功过渡到独立的巨大潜力，这体现在他的研究生产力、高质量的研究出版物、奖项和荣誉上。他目前的职业目标是开发前列腺癌的新绷带治疗方法，并成功过渡到独立。他的长期目标是开发一项国际公认的纳米技术在放射治疗中的应用研究计划。KO1奖将为开展拟议的研究和补充的教学和临床培训部分提供受保护的时间环境：机构环境、Dana-Farber癌症研究所(DFCI)、哈佛医学院最适合进行候选人的拟议研究和职业发展。我们有必要的教学、临床和研究资源，并有关键的教师与之合作。研究：拟议研究的总体目标是开发一种新的近距离放射治疗应用，通过金纳米颗粒洗脱剂(绷带)进行原位剂量涂抹，以绕过目前挽救前列腺癌放射治疗和辐射增强的关键障碍。Bandage试图通过将放射增敏(BUT)生物相容金纳米颗粒(AuNP)装载到常规使用的近距离放射治疗间隔物中来绕过这些关键限制，这些纳米颗粒可以在植入前列腺肿瘤后在原位释放/洗脱。例如，可以通过改变AuNP大小、间隔物位置、浓度和其他参数来定制AuNP从间隔物原位释放以及随之而来的三维肿瘤内随时间的生物分布，以在不增加对健康组织的毒性的情况下提供亚体积AuNP辅助的前列腺放射增强。这项K01应用的中心假设是，用于前列腺癌治疗的新绷带是挽救放射治疗和增强辐射的更有效的方法，因为可以在不增加正常组织毒性的情况下进行可定制的亚体积增强。具体目标是：1)在临床前模型中建立可定制的肿瘤内生物分布概况和从载金近距离治疗间隔物中释放的金纳米颗粒(AuNP)的药代动力学；2)在临床前模型中使用绷带显示显著的治疗增强；3)开发前列腺癌绷带治疗计划软件工具。与NCI的使命相关，该项目的预期成果包括：为前列腺癌患者开发可能改进的治疗方案(绷带)，以及将申请者的职业发展成为与癌症作斗争的成功和富有成效的独立调查者。

DESCRIPTION (provided by applicant): The candidate has demonstrated great potential to successfully transition into independence as evinced by his research productivity, high quality of research publications, awards, and honors. His immediate career goal is to develop the new BANDAGE for prostate cancer treatment approach and successfully transition into independence. His long term goal is to develop an internationally recognized research program in applications of nanotechnology in radiation therapy. The KO1 award will provide protected time for carrying out the proposed research and complementary didactic and clinical training components Environment: The institutional environment, Dana-Farber Cancer Institute (DFCI), Harvard Medical School is optimally suitable for conducting the proposed research and career development of the candidate. The necessary didactic, clinical and research resources are available together with key faculty to work with. Research: The overall goal of the proposed research is to develop a new brachytherapy application with in situ dose-painting administered via gold-nanoparticle eluters (BANDAGE) that would circumvent current critical barriers to salvage radiotherapy and radiation boosting for prostate cancer. BANDAGE seeks to circumvent these critical limitations by loading routinely used brachytherapy spacers with radio-sensitizing (but) biocompatible gold nanoparticles (AuNP), which can be released/eluted in situ after implantation in prostate tumors. The AuNP release, in situ, from the spacers and consequent 3-dimensional intra-tumor bio-distribution over time may be customized e.g. by varying AuNP size, spacer position, concentration, and other parameters to provide sub-volume AuNP-aided radiation boosting of the prostate without increased toxicity to healthy tissue. The central hypothesis of this K01 application is that the new BANDAGE for prostate cancer treatment modality is a more efficacious approach for salvage radiotherapy and radiation boosting, because of the potential for customizable sub-volume boosting without increase in normal tissue toxicity. The specific aims are: 1) Establish customizable intra-tumor biodistribution profiles and pharmacokinetics of gold nanoparticles (AuNP) released from gold-loaded brachytherapy spacers in pre-clinical models; 2) Demonstrate significant therapeutic enhancement using BANDAGE in preclinical models; 3) Develop treatment planning software tools for BANDAGE for prostate cancer. Relevant to the mission of the NCI, the expected outcomes of this project include: development of potentially improved treatment option (BANDAGE) for prostate cancer patients, and career development of the applicant into a successful and productive independent investigator in the fight against cancer.