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

描述（由申请人提供）：该候选人具有成功过渡到独立的巨大潜力，其研究生产力，高质量的研究出版物，奖项和荣誉证明了这一点。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。他的长期目标是在纳米技术在放射治疗中的应用方面发展一个国际公认的研究项目。KO1奖将为进行拟议的研究和补充教学和临床培训部分提供保护时间。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拟议的研究和候选人的职业发展。这里有必要的教学、临床和研究资源，还有重要的教师。研究：该研究的总体目标是开发一种新的近距离治疗应用，通过金纳米颗粒洗脱器（绷带）进行原位剂量涂敷，以绕过目前前列腺癌补救性放疗和辐射增强的关键障碍。绷带试图通过在常规的近距离治疗间隔器中装载具有放射致敏（但）生物相容性的金纳米颗粒（AuNP）来规避这些关键限制，这些纳米颗粒在植入前列腺肿瘤后可以原位释放/洗脱。间隔剂的AuNP原位释放和随后的三维肿瘤内生物分布可以随时间定制，例如，通过改变AuNP大小、间隔剂位置、浓度和其他参数，提供亚体积AuNP辅助前列腺辐射增强，而不会增加对健康组织的毒性。这项K01应用的中心假设是，新的前列腺癌治疗方式是一种更有效的补救性放疗和辐射增强方法，因为有可能在不增加正常组织毒性的情况下进行可定制的亚容量增强。具体目标是：1)在临床前模型中建立可定制的近距离治疗金纳米颗粒（AuNP）在肿瘤内的生物分布特征和药代动力学；2)在临床前模型中证明使用绷带显著增强治疗效果；3)开发前列腺癌绷带治疗计划软件工具。与NCI的使命相关，该项目的预期结果包括：为前列腺癌患者开发潜在的改进治疗方案（绷带），并将申请人的职业发展成为与癌症作斗争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.