FREQUENCY-DEPENDENT EFFECTS OF ULTRASOUND-GUIDED FERROPTOSIS IN OVARIAN AND BREAST CANCER: IMPLICATIONS FOR TARGETED SONOTHERAPY, RECOVERY, AND PHYSICAL FUNCTION

Abstract

Background: Low-intensity ultrasound (LIUS) is an emerging, non-invasive therapeutic strategy with potential applications in targeted cancer treatment, functional recovery, and sports medicine. However, the mechanisms underlying its frequency-dependent effects on tumor suppression remain partially understood, particularly in relation to cell-type specificity and ferroptosis induction. This study investigates the role of LIUS frequency in modulating ferroptotic pathways, focusing on its effects in ovarian (SKOV3) and breast (MDA-MB-231) cancer cells, with potential implications for minimizing systemic toxicity and preserving post-treatment physical function. Methods: A frequency-optimized LIUS protocol (0.3 W/cm², within acoustic safety limits) was applied to evaluate tumor suppression efficiency and ferroptosis induction. The study identified 800 kHz and 600 kHz as the most effective frequencies for ovarian and breast cancer cell inhibition, respectively, leading to enhanced ferroptotic activity. To potentiate these effects, PEG-coated magnetic iron oxide nanoparticles (Fe₃O₄@PEG) were integrated, facilitating p53-mediated ferroptotic pathways and maximizing tumor suppression. In vivo experiments were conducted to assess tumor inhibition, therapeutic safety, and the impact on systemic recovery and functional adaptation. Results: The combination of LIUS and Fe₃O₄@PEG nanoparticles significantly enhanced tumor suppression with minimal off-target effects, demonstrating a tumor growth inhibition rate of up to 92%. Notably, the study confirmed that frequency-specific LIUS modulation plays a crucial role in determining cell-type selectivity and therapeutic efficacy, suggesting potential applications in precision oncology and rehabilitation medicine. Conclusion: This study provides strong evidence for the use of LIUS as a frequency-dependent, ferroptosis-inducing strategy for targeted cancer therapy, with minimal systemic side effects and implications for post-treatment recovery. The integration of Fe₃O₄@PEG nanoparticles enhances therapeutic precision, offering a cell-selective, minimally invasive approach to tumor suppression. Given the growing interest in non-invasive modalities that preserve physiological integrity, LIUS-based therapies may have valuable applications in sports medicine and rehabilitation, supporting oncology patients in maintaining functional mobility and optimizing post-treatment physical performance. Future research should explore the role of ultrasound-guided therapies in promoting tissue regeneration, mitigating fatigue, and improving neuromuscular recovery in cancer survivors.