The toxic effects of doxorubicin (DOX) on the heart limit the dose that can be administered systemically for the treatment of solid tumors. Targeted delivery of DOX to solid tumors will localize its cytotoxic effects, and improve its therapeutic index. This can be achieved by encapsulating DOX in temperature-sensitive liposomes and triggering release via ultrasound-induced heating in tumors. These DOX-loaded liposomes (diameter < 200 nm) can extravasate through leaky tumor vasculature and

more »

... late in the tumor interstitium. High intensity focused ultrasound can be used to heat the tumors noninvasively and trigger DOX release from the temperature-sensitive liposomes. By coencapsulating manganese sulfate in the liposomes, MRI can be used to monitor temperature-induced drug release from the liposomes. Manganese is a molecule that self-quenches when encapsulated in liposomes, but provides a strong MR signal when released. Thus, MR imaging can be used to provide feedback control of the transducer output to ensure sufficient heating and optimal DOX release at the breast tumor site. MRI-guided localized delivery of DOX to solid tumors will potentially raise the therapeutic index of DOX, thus reducing the required dose and frequency of drug administered systemically for tumor regression.