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: 7563799
• 负责人: Agata A Exner
• 金额: $ 40.54万
• 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 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7563799
• 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; Fever; Fluorescence Microscopy; Focused Ultrasound Therapy; Future; Gases; Glioma; Growth; Heat shock proteins; Heating; High Pressure Liquid Chromatography; Histology; Human; 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. Public Health Relevance: Our study evaluates a new approach for the improvement of image-guided radiofrequency (RF) ablation of tumors which uses a nontoxic thermosensitizer entrapped in a multifunctional delivery vehicle to increase the susceptibility of cancer cells to heat-related stress. This technique may overcome one of the primary hurdles of focused hyperthermia treatment - the inability to completely destroy the entire tumor volume -- a problem due, in part, to the recovery of cancerous cells which receive sub-lethal levels of heat at the tumor periphery. This project addresses this unmet need with a mild, nontoxic agent delivered in a lipid nanoparticle that attacks these cells and leads to their total eradication and which permits noninvasive therapy tracking using ultrasound. The use of readily-available and safe agents for this application may allow rapid translation of this work to clinical studies, resulting in more effective patient care.

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。 公共健康相关性：我们的研究评估了一种改进图像引导射频（RF）肿瘤消融的新方法，该方法使用多功能递送载体中包埋的无毒热敏剂来增加癌细胞对热相关应激的敏感性。这项技术可以克服集中热疗治疗的主要障碍之一——无法完全破坏整个肿瘤体积——这一问题部分是由于癌细胞在肿瘤周边接受亚致死水平的热量而恢复的。 。该项目通过在脂质纳米颗粒中提供温和、无毒的药剂来解决这一未满足的需求，该药剂可以攻击这些细胞并导致其完全根除，并允许使用超声波进行无创治疗跟踪。在该应用中使用现成且安全的药物可以使这项工作快速转化为临床研究，从而实现更有效的患者护理。