Targeted Docetaxel-Nanocolloid for the Treatment of Ovarian Cancer

描述（由申请人提供）：项目总结本提案是响应国家卫生研究所小企业创新研究（SBIR）计划呼吁的第1阶段提案，该计划呼吁通过纳米技术（SBIR [U43/U44]）[计划公告编号：PA-10-286]进行癌症诊断和治疗。 Nemucore Medical Innovation，Inc. NMI公司（NMI）的这一1期SBIR提案的目标是充分确定包裹在纳米胶体中的新型整联蛋白v3和v5靶向多西他赛（DTX）的控释、靶向、细胞毒性、药代动力学和疗效特征，该纳米胶体用专有的逐层制造工艺制成，命名为NMI-700，用于治疗表达整联蛋白的卵巢癌。NMI的长期目标是将NMI-700与利用AutoGenomic的INFINITI”平台的伴随诊断相结合，以筛选表达整合素的卵巢肿瘤，以便将患者分层到最受益于这种独特治疗的队列中。标准化疗药物的部分挑战是药物的保留和分布，这可以通过使用NMI的长循环纳米胶体技术来解决，该技术用于封装难溶性药物，如DTX。整合素靶向高度适用于卵巢癌，因为与其他成人组织相比，大多数卵巢癌差异表达整合素。因此，NMI-700的设计结合了许多关键属性，这些属性通过减轻溶解度问题来响应DTX的物理限制，并通过靶向和受控释放螯合的DTX来响应限制全身暴露的临床观察结果，从而降低药物毒性、清除和失活。 对于新诊断的卵巢癌患者，其中大多数人迅速发展到化疗耐药状态，NMI的纳米医学提供了一种解决方案，迫切需要治疗难治性疾病的患者，这通常是无法治愈的， 进一步的治疗从治愈转变为姑息。预计临床前研究将推进到后续临床试验，在临床试验中，将使用伴随的INFINITI诊断将患者分为潜在应答者。到授权期结束时，NMI应该有大量的数据需要进行下一阶段的临床前开发，并进一步推进这种独特的整合素靶向/DTX纳米医学进入临床。NMI预计NMI-700产品的开发将提供以下益处：为迫切需要临床解决方案的患者群体的肿瘤提供新的高细胞毒性治疗。推进纳米医学的发展，这是对个性化医疗承诺的关键补充。商业化一种新的制造方法，用于溶解难溶性药物。

DESCRIPTION (provided by applicant): PROJECT SUMMARY This proposal is a Phase 1 proposal in response to The National Institute of Health Small Business Innovation Research (SBIR) Program call for proposals for the Cancer Diagnostics and Therapeutic Agents Enabled By Nanotechnology (SBIR [U43/U44]) [Program Announcement Number: PA-10-286]. Nemucore Medical Innovation, Inc.'s (NMI) goal for this Phase 1 SBIR proposal is to fully determine the controlled release, targeting, cytotoxicity, pharmacokinetics, and efficacy profile for a novel integrins v3 and v5 targeted docetaxel (DTX) encased in a nanocolloid created with a proprietary layer-by-layer manufacturing process, designated NMI-700, for treatment of integrin expressing ovarian cancers. NMI's long- term goal is to couple NMI-700 with a companion diagnostic utilizing AutoGenomic's INFINITI" platform to screen for integrin expressing ovarian tumors in order to stratify patients into a cohort who would most benefit from this unique treatment. Part of the challenge with standard chemotherapeutic agents is the retention and distribution of the agent, which can be solved with the use of the NMI's long circulating nanocolloid technology developed for encapsulating poorly soluble drugs, such as DTX. Integrin targeting is highly applicable for ovarian cancer because most of ovarian cancers differentially express integrins compared to other adult tissues. Therefore design of NMI-700 incorporates a number of key attributes, which respond to physical limitations of DTX by mitigating solubility issues and to clinical observations that limiting systemic exposure that reduces drug toxicity, clearance, and inactivation through targeting and controlled release of sequestered DTX. For newly diagnosed ovarian cancer patients, a majority of whom rapidly progress to a chemoresistant state, NMI's nanomedicine offers a solution that is urgently needed for treating patients with refractory disease, which is generally incurable, and the goal of further treatment changes from one of cure to one of palliation. It is anticipated that the pre-clinical studies will advance to subsequent clinical trials where patients will be segregated into potential responders using the companion INFINITI" diagnostic. By the end of the grant period NMI should have much of the data needed to proceed to the next stage of preclinical development and to further the advancement of this unique integrin-targeted/DTX nanomedicine into the clinic. NMI anticipates that development of NMI-700 product will provide the following benefits: ¿ Provide a new highly cytotoxic treatment for tumors of a patient population in desperate need for a clinical solution. ¿ Advance the development of nanomedicine, a key compliment to the promise of personalized medicine. ¿ Commercialize a new method of manufacture for solubilizing poorly soluble drugs.