Generation of micro-nano bubbles by magneto induced internal heat for protecting cells from intermittent hypoxic damage

Micro-nano bubbles (MNBs) have attracted extensive attention in recent years due to their distinctive features and physiological activities. The particle size and size distribution of MNBs are important properties of their application. This study presented a green method, namely magneto internal heat bubble generation (MIHBG), for preparing magnetic MNBs based on the magnetically internal heating technology. The effects of the operation conditions on the properties of the generated MNBs were discussed. The results showed that the MNBs with good uniformity could be successfully prepared via MIHBG. Under the preferred conditions, the average size of the MNBs was 341.5 ± 18.2 nm with the polydispersity index (PDI) of 0.240 ± 0.027 and the zeta potential of − 42.4 ± 4.2 mV, respectively. The concentration of the generated MNBs could reach 1.5 × 109 particles/mL. Transmission electron microscopy (TEM) image demonstrated that the MNBs had a gas core with the superparamagnetic iron oxide nanoparticles (SPIONs) adsorbed on the surface. The mechanism of the MNBs generation process was explained by the classical nucleation theory. The good uniformity of the magnetic MNB samples benefited from the uniform hotspots formed by the SPIONs via the alternating magnetic field. In addition, the lipid-encapsulated Xenon bubbles (Xe-LBs) were prepared based on the MIHBG process to improve the stability of MNBs for the determination of protecting cells from intermittent hypoxic damage. MTT assay and TUNEL experiments indicated that the Xe-LBs played a significant role in protecting cells from intermittent hypoxic damage and inhibiting apoptosis of cells. These results revealed that the MIHBG process provided a novel way to prepare MNBs for potential applications such as protecting hypoxic neurons.