Sensitizer Delivery for Focused Hyperthermia Cancer Treatment

用于癌症集中热疗治疗的敏化剂输送

• 批准号: 8433241
• 负责人: Agata A Exner
• 金额: $ 34.23万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8433241
• 关键词: Ablation; Address; Adjuvant; Adopted; Aftercare; Area; Biocompatible Materials; Biological; Blood Vessels; Brain; Cancer Biology; Cancerous; Cell Culture Techniques; Cell membrane; Cells; Clinical; Clinical Research; Coagulative necrosis; Contrast Media; Data; Dependence; Deposition; Development; Dose; Electrodes; Electron Transport; Ensure; Ethylene Oxide; Excision; Fluorescence Microscopy; Focused Ultrasound Therapy; Future; Gases; Glioma; Growth; Heat shock proteins; Heating; High Pressure Liquid Chromatography; Histology; Human; Hyperthermia; Image; Image Analysis; Image Enhancement; In Vitro; Injury; Interventional radiology; Investigation; Kidney; Kinetics; Label; Large Intestine Carcinoma; Lasers; Lead; Left; Lipids; Local Hyperthermia; Malignant Neoplasms; Membrane Lipids; Microbubbles; Microscopy; Modeling; Molecular; Molecular Weight; Nature; Needles; Normal Cell; Normal tissue morphology; Nude Mice; Operative Surgical Procedures; Patient Care; Peripheral; Permeability; Pharmacologic Substance; Pluronics; Polymers; Predisposition; Production; Property; Protocols documentation; Radiofrequency Interstitial Ablation; Rattus; Recovery; Recurrence; Research; Residual Tumors; Role; Safety; Scheme; Science; Site; Stress; Structure; System; Techniques; Technology; Time; Translations; Treatment Efficacy; Tumor Tissue; Tumor Volume; Ultrasonography; Work; alternative treatment; cancer cell; cancer therapy; chemotherapy; copolymer; efficacy testing; hyperthermia treatment; improved; in vivo; insight; interest; light scattering; microwave electromagnetic radiation; minimally invasive; nanoparticle; neoplastic cell; novel strategies; particle; phosphatidylserine receptor; poly(propylene oxide); prevent; protein expression; public health relevance; radiofrequency; research study; success; surfactant; targeted delivery; treatment response; tumor; tumor progression; uptake

DESCRIPTION (provided by applicant): Image guided radiofrequency (RF) ablation, a minimally-invasive approach which utilizes locally applied energy to induce coagulative necrosis in tumors, has become a reliable alternative treatment of cases where surgical resection of the tumor is not a feasible option. Despite the demonstrated successes, unresolved issues such as peripheral cooling of tumor tissue near major blood vessels, restricted size of the energy deposition, and seeding of residual tumor around needle electrode track, have all been shown to be causes of incomplete treatments leading to local tumor re-growth. We propose to explore a unique biomaterial / pharmaceutical approach to overcome these concerns and ensure a reproducible, successful ablation treatment. Through research uniting cancer biology, interventional radiology, and biomaterials science, this proposal will investigate local delivery of poly (ethylene oxide)-poly (propylene oxide) block copolymers for the enhancement of image guided RF ablation of tumors. Preliminary experiments have demonstrated that these nonionic surfactants have the potential to increase the susceptibility of cancer cells to heat-related injury, while leaving normal cells unharmed. We thus hypothesize that ablation combined with this a sensitizing pretreatment delivered via lipid nanoparticles to the site of action will be a superior treatment to radiofrequency ablation alone. Upon successful completion, the proposed research should result in improved efficacy of local tumor radiofrequency ablation. The proposal may also lead to further insight into the interesting effects of nonionic surfactant molecules on cancer treatment and hyperthermia, opening doors to future investigations into the field.

描述（由申请人提供）：图像引导射频（RF）消融是一种微创方法，利用局部施加的能量诱导肿瘤凝固性坏死，已成为无法手术切除肿瘤的病例的可靠替代治疗方法选项。尽管取得了成功，但尚未解决的问题，例如主要血管附近肿瘤组织的外围冷却、能量沉积的尺寸受限以及针电极轨道​​周围残留肿瘤的播种，都已被证明是导致局部肿瘤的不完整治疗的原因重新生长。我们建议探索一种独特的生物材料/药物方法来克服这些问题并确保可重复、成功的消融治疗。通过结合癌症生物学、介入放射学和生物材料科学的研究，该提案将研究聚环氧乙烷-聚环氧丙烷嵌段共聚物的局部递送，以增强图像引导的肿瘤射频消融。初步实验表明，这些非离子表面活性剂有可能增加癌细胞对热相关损伤的敏感性，同时使正常细胞不受伤害。因此，我们假设消融与通过脂质纳米粒子递送到作用部位的敏化预处理相结合将是比单独射频消融更好的治疗方法。成功完成后，拟议的研究将提高局部肿瘤射频消融的疗效。该提案还可能进一步深入了解非离子表面活性剂分子对癌症治疗和热疗的有趣影响，为该领域的未来研究打开大门。

项目成果

Applications of ultrasound for image-guided drug delivery in cancer chemotherapy.

超声在图像引导药物输送在癌症化疗中的应用。

• 发表时间: 2013-07
• 影响因子: 4.2
• 作者: Solorio, Luis;Exner, Agata A
• 通讯作者: Exner, Agata A

Agarose gel stiffness determines rate of DRG neurite extension in 3D cultures.

琼脂糖凝胶硬度决定 3D 培养物中 DRG 神经突延伸的速率。

• DOI: 10.1016/s0142-9612(00)00350-1
• 发表时间: 2001-05-01
• 期刊: Biomaterials
• 影响因子: 14
• 作者: A. Balgude;Xiaojun Yu;A. Szymanski;R. Bellamkonda
• 通讯作者: R. Bellamkonda

Role of Pluronic block copolymers in modulation of heat shock protein 70 expression.

Pluronic 嵌段共聚物在调节热休克蛋白 70 表达中的作用。

• 发表时间: 2011
• 作者: Perera RH;Krupka TM;Wu H;Traughber B;Dremann D;Broome AM;Exner AA
• 通讯作者: Exner AA

Time and dose dependence of pluronic bioactivity in hyperthermia-induced tumor cell death.

热疗诱导的肿瘤细胞死亡中普朗尼克生物活性的时间和剂量依赖性。

• 发表时间: 2009-01
• 作者: Krupka, Tianyi M;Dremann, David;Exner, Agata A
• 通讯作者: Exner, Agata A

Ultrasound imaging beyond the vasculature with new generation contrast agents.

使用新一代造影剂进行超越脉管系统的超声成像。

• DOI: 10.1002/wnan.1326
• 发表时间: 2015-07
• 期刊: Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
• 影响因子: 8.6
• 作者: Perera, Reshani H.;Hernandez, Christopher;Zhou, Haoyan;Kota, Pavan;Burke, Alan;Exner, Agata A.
• 通讯作者: Exner, Agata A.