Combination of magnetic resonance-guided focused ultrasound and polymer-modified thermosensitive liposomes for cancer therapy

In this study, the response of solid tumors implanted in rat hindlimbs to doxorubicin (DOX) released locally from a novel polymer-modified thermosensitive liposome (pTSL) was investigated. The pTSL was engineered to release encapsulated DOX at lower thermal doses than traditional thermosensitive liposomes. Rat mammary adenocarcinoma cells were implanted in the hindlimb of healthy rats and allowed to grow to at least 100 mm³. DOX-loaded pTSL were injected intravenously and allowed to accumulate in the tumor interstitium over several hours. MR-guided 1.7-MHz focused ultrasound (MRgFUS) was used to heat the tumor volume and trigger the release of encapsulated DOX. Acoustic parameters (i.e. acoustic power, pulse duration, etc.) were identified to heat and maintain tumors at 40°C or 43°C for five minutes. Treatment with DOX-loaded pTSL and MRgFUS-mediated heating significantly reduced the rate of tumor growth. The response of tumors to DOX released from pTSL at 43°C was comparable to the response of tumors treated with unencapsulated DOX. The results of this study demonstrate that solid tumors can be treated successfully with DOX-loaded thermosensitive liposomes and MRgFUS with negligible toxic effects.