Plasma Generation of Aqueous Chemotherapeutic Solutions

水性化疗溶液的等离子体生成

• 批准号: 9200490
• 负责人: Jessica Joslin
• 金额: $ 22.49万
• 依托单位: SYMBIOS TECHNOLOGIES, INC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9200490
• 关键词: Address; AlamarBlue; Animal Cancer Model; Animal Model; Apoptosis; Arts; Biological Assay; Cancer Cell Growth; Cancer cell line; Cancerous; Caspase; Catheters; Cause of Death; Cell Culture Techniques; Cell Death; Cell Line; Cells; Chemistry; Chemotherapy-Oncologic Procedure; Clinical; Data; Diagnosis; Disease; Dose; Endothelial Cells; Exhibits; Flow Cytometry; Gases; Generations; Goals; Growth; Half-Life; Hydrogen Peroxide; Inhibition of Cancer Cell Growth; Investigation; Life; Literature; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Medicine; Methods; Modality; Modification; Necrosis; Nitrates; Nitrites; Normal Cell; Oxidants; Ozone; Pancreas; Pathway interactions; Patients; Phase; Plasma; Production; Property; Proteins; Reaction; Resistance; Route; Running; Serum; Site; Small Business Innovation Research Grant; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Topical application; Treatment Efficacy; Tubular formation; United States; Work; aqueous; base; cancer cell; cancer therapy; cancer type; chemotherapy; cold temperature; combinatorial; commercialization; flexibility; gemcitabine; improved; in vivo; innovation; insight; killings; novel; novel therapeutics; pancreatic cancer cells; research study; residence; response; standard care; success; tumor

Despite significant advances in chemotherapeutic approaches due to new drugs and combinatorial therapies over the past decades, cancer is still the second leading cause of death in the United States. Further, pancreatic cancer is one of the most aggressive and deadly cancer types, with only a 7% chance of patient survival five years past diagnosis. In this Phase I SBIR proposal, the Tubular Plasma ReactorTM (TPR) platform developed by Symbios Technologies, Inc. will be used to generate reactive plasma species in aqueous solutions via a low-temperature plasma discharge. This technology encompasses the formation of aqueous plasma chemotherapeutic (APC) solutions, which are intended to be applied for selective pancreatic cancer cell modification to address critical cancer therapy needs. The TPR platform enables the environmentally friendly production of APC to provide clinicians with the flexibility of multiple routes of administration. The formation of plasma species within aqueous solutions sets TPR- generated APC apart from other plasma-based technologies. More specifically, previous work has shown that the use of gas-phase plasma plumes directed on cell cultures resulted in the selective inhibition of pancreatic cancer cell growth, while not harming normal endothelial cells. However, such gas-phase plumes restrict the use to topical applications, which are not useful for the treatment of internal tumors. Preliminary data collected by Symbios Technologies employing TPR-generated APC demonstrates the selective, dose-dependent treatment of cancer cells, while normal cells remained viable across all doses. Thus, this proposal is focused on four major goals: (a) optimize APC generation for maximum therapeutic efficacy, (b) expand the investigation of APC to multiple pancreatic cancer lines that exhibit differences in resistance to the current standard treatment, (c) quantify the relevant stable plasma species that contribute to the therapeutic action to inform mechanistic insights and to evaluate shelf-life and serum scavenging, and (d) identify the mechanism of action associated with APC inhibition of cancer cell growth. Overall, the APC preliminary data collected combined with previous literature regarding the therapeutic properties of plasma species supports the hypothesis that the TPR represents a viable platform for generating chemotherapeutic solutions. Thus, Symbios will be the first to combine aqueous plasma chemistry with chemotherapeutic effects to result in a commercially viable cancer treatment modality. Completion of Phase I objectives will make possible in vivo animal cancer models in Phase II.

尽管由于新药物的出现，化学治疗方法取得了重大进展， 在过去的几十年里，癌症仍然是第二大死亡原因， 在美国此外，胰腺癌是最具侵袭性和致命性的癌症之一， 类型，只有7%的机会，病人生存五年后诊断。在本阶段I SBIR中， 提案是Symbios Technologies开发的管状等离子体反应器TM（TPR）平台， Inc.将用于通过低温等离子体技术在水溶液中产生活性等离子体物质， 等离子体放电该技术包括水等离子体的形成 化疗（APC）溶液，其旨在应用于选择性胰腺癌。 癌细胞修饰以解决关键的癌症治疗需求。TPR平台使 APC的环保生产，为临床医生提供多种 给药途径。水溶液中等离子体物质的形成设定TPR- 除了其他基于等离子体的技术之外，更具体地说，以前的工作 已经表明，使用直接作用于细胞培养物的气相等离子体羽流， 选择性抑制胰腺癌细胞生长，同时不损害正常内皮细胞。 然而，这样的气相羽流限制了局部应用的使用，这对于局部应用是无用的。 内部肿瘤的治疗。Symbios Technologies使用 TPR产生的APC显示出对癌细胞的选择性、剂量依赖性治疗， 正常细胞在所有剂量下保持存活。因此，本建议侧重于四个主要目标： (a)优化APC产生以获得最大治疗功效，（B）扩大对 APC对表现出对电流的抗性差异的多种胰腺癌细胞系的作用 标准处理，（c）量化有助于产生稳定血浆的相关稳定血浆物质。 治疗作用，以提供机制见解并评价保质期和血清清除， 和（d）鉴定与APC抑制癌细胞生长相关的作用机制。 总的来说，APC收集的初步数据与以前的文献相结合， 血浆物质的治疗特性支持TPR代表一种可行的 用于产生化疗溶液的平台。因此，Symbios将是第一个将联合收割机 具有化疗效果的水性等离子体化学， 癌症治疗模式。I期目标的完成将使体内动物实验成为可能。 第二阶段的癌症模型。

项目成果

Aqueous Plasma Pharmacy: Preparation Methods, Chemistry, and Therapeutic Applications.

• DOI: 10.1615/plasmamed.2016018618
• 发表时间: 2016-01-01
• 期刊: Plasma medicine
• 作者: Joslin, Jessica M;McCall, James R;Hybertson, Brooks M
• 通讯作者: Hybertson, Brooks M