Tumor-specific aggregation of magnetic liposome nanoparticles in tumor-bearing mice after ultrasound-guided intratumor injection of liquid-solid phase-change biomagnetic material

Abstract

Objective To prepare ultrasound-guided intratumor injection of liquid-solid phase-transition biomagnetic material (NdFeB/Fe3O4/PLGA, NFP) and investigate its feasibility and efficiency of aggregating for targeted aggregation of intravenously injected magnetic liposome nanoparticles (MLPs). Methods The biomagnetic material NFP was prepared and its liquid-solid phase transition ability, morphology and magnetization performances were assessed; the form, particle size and diameter of MLPs were also characterized. The biocompatibility of NFP and MLPs were evaluated by cytotoxic proliferation experiments, and the efficiency of MLP capture by NFP was determined using an in vitro model of extracorporeal circulation. A 4T1 mouse model bearing breast cancer xenograft was established, in which NFP was injected in the tumor under ultrasound guidance and MLPs conjugated with a fluorescent dye was injected intravenously by tail vein. The efficiency of NFP implant for capturing the MLPs for targeted aggregation of the latter in the xenograft was evaluated using in vivo fluorescence imaging. Results The biomagnetic material NFP capable of liquid-solid phase transition was successfully prepared. Scanning electron microscopy and elemental mapping results showed a homogeneous distribution of the elements in NFP after phase transition. The NFP implant could be efficiently magnetized in vitro, and the magnetic forces of NFP was positively correlated with its volume (350.14±23.89, 493.47±19.54, 679.39±34.23, and 812.36±27.99 Gs for 25, 50, 75, and 100 μL of NFP, respectively). The prepared MBLs had a uniform particle size of 373.658±50.000 nm with a zeta potential of -24.8±2.5 mV. Cytotoxicity experiments with tumor cells and normal cells showed no obvious cytotoxicity of either NFP or MLPs. in vivo fluorescence imaging showed that following intravenous MLB injection and intratumor NFP implantation, the fluorescence intensity was significantly enhanced in the xenografts in the tumor-bearing mice. Conclusion The prepared liquid-solid phase-change biomagnetic NFP and the MLPs have good biocompatibility. NFP implantation in the tumor can efficiently capture intravenously injected MLPs to achieve targeted aggregation of MLPs in the tumors.

Keywords

• biomagnet
• magnetic target
• nanoparticles targeting drug delivery
• magnetic liposome
• ultrasound
• nanoparticles