Four Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) thermal therapy strategies (no HIFU, hyperthermia, ablation and hyperthermia followed by ablation) in combination with temperature sensitive liposomes (TSLs), co-encapsulating doxorubicin (dox) and ProHance®, were investigated in rhabdomyosarcoma rat tumor model. All HIFU heating strategies combined with TSLs resulted in cellular uptake of dox deep into the interstitial space and significant increase of intratumoral drug concentrations. The combination of hyperthermia-triggered TSLs followed by ablation showed the best therapeutic outcome compared to other strategies due to direct induction of thermal necrosis in the tumor core and efficient drug delivery to the tumor rim.
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