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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Gene and Drug Delivery Systems Study Section (GDD)
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Tandon, Pushpa
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Case Western Reserve University
Schools of Medicine
United States
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Perera, Reshani H; Solorio, Luis; Wu, Hanping et al. (2014) Nanobubble ultrasound contrast agents for enhanced delivery of thermal sensitizer to tumors undergoing radiofrequency ablation. Pharm Res 31:1407-17
Perera, Reshani H; Patel, Ravi; Wu, Hanping et al. (2013) Preclinical evaluation of radiosensitizing activity of Pluronic block copolymers. Int J Radiat Biol 89:801-12
Wu, Hanping; Rognin, Nicolas G; Krupka, Tianyi M et al. (2013) Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents. Ultrasound Med Biol 39:2137-46
Wu, Hanping; Patel, Ravi B; Zheng, Yuanyi et al. (2012) Differentiation of benign periablational enhancement from residual tumor following radio-frequency ablation using contrast-enhanced ultrasonography in a rat subcutaneous colon cancer model. Ultrasound Med Biol 38:443-53
Perera, Reshani H; Krupka, Tianyi M; Wu, Hanping et al. (2011) Role of Pluronic block copolymers in modulation of heat shock protein 70 expression. Int J Hyperthermia 27:672-81
Krupka, Tianyi M; Exner, Agata A (2011) Structural parameters governing activity of Pluronic triblock copolymers in hyperthermia cancer therapy. Int J Hyperthermia 27:663-71
Krupka, Tianyi M; Solorio, Luis; Wilson, Robin E et al. (2010) Formulation and characterization of echogenic lipid-Pluronic nanobubbles. Mol Pharm 7:49-59