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

描述（由申请人提供）：候选人已表现出巨大的潜力，成功地过渡到独立，他的研究生产力，高质量的研究出版物，奖项和荣誉证明。他的近期职业目标是开发新的前列腺癌治疗方法，并成功过渡到独立。他的长期目标是发展一个国际公认的研究计划，在纳米技术在放射治疗中的应用。KO 1奖将为开展拟议的研究和补充教学和临床培训部分提供受保护的时间环境：哈佛医学院丹娜-法伯癌症研究所（DFCI）的机构环境最适合进行候选人的拟议研究和职业发展。必要的教学，临床和研究资源可与关键教师一起工作。调研：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，通过金纳米粒子洗脱器（BANDAGE）进行原位剂量绘画，以规避目前挽救前列腺癌放射治疗和放射增强的关键障碍。BANDAGE试图通过将放射增敏（但）生物相容性金纳米颗粒（AuNP）装载到常规使用的近距离放射治疗间隔器中来规避这些关键限制，这些纳米颗粒可以在植入前列腺肿瘤后原位释放/洗脱。可以例如通过改变AuNP尺寸、间隔物位置、浓度和其他参数来定制AuNP从间隔物的原位释放和随后的随时间的三维肿瘤内生物分布，以提供前列腺的子体积AuNP辅助的辐射增强，而不增加对健康组织的毒性。该K 01申请的中心假设是，用于前列腺癌治疗模式的新BANDAGE是挽救性放疗和辐射增强的更有效方法，因为其具有可定制的子体积增强而不增加正常组织毒性的潜力。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曲线和从载金近距离放射治疗间隔器释放的金纳米颗粒（AuNP）的药代动力学; 2）在临床前模型中使用BANDAGE证明显著的治疗增强; 3）开发用于前列腺癌的BANDAGE的治疗计划软件工具。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潜在的改进治疗方案（BANDAGE），以及将申请人的职业发展成为对抗癌症的成功和富有成效的独立研究者。

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.