Gas-Filled Phospholipid Nanoparticles Conjugated with Gadolinium Play a Role as a Potential Theragnostics for MR-Guided HIFU Ablation

To develop a long-circulating theragnostics, meaning therapeutics and diagnostics for MR-guided HIFU ablation, we designed and prepared Gd-C5F12-phospholipid nanobubbles (PLNs) 30–100 nm in diameter. The biochemical and physical characterization of Gd-C5F12-PLNs were performed. Since Gd-C5F12-PLN-50 (Φ = 50 nm) and Gd-C5F12-PLN-100 (Φ = 100 nm) enhanced the hyperthermal effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom, its circulation, distribution, tumor accumulation and tumor ablation were examined in tumor-bearing mice. The plasma-half life of Gd-C5F12-PLNs was longer than 1.5 hrs. Gd-C5F12-PLNs mainly accumulated in the liver and the spleen, suggesting that they are slowly secreted through the hepatobiliary pathway. Monitored by the T1 signal intensity of MR, Gd-C5F12-PLNs accumulated in tumor tissues for 8 hours in mice. HIFU with Gd-C5F12-PLN-100 showed the increased tumor ablation area as compared with HIFU alone. The results suggest that Gd-C5F12-PLNs exhibit a potential theragnostics for MR-guided HIFU ablation.