To prepare SDF-1 α-loaded nanoliposome (SNP)-SonoVue complex and investigate its tracing abilities, sustained-release property and effect on migration of bone marrow mesenchymal stem cells (BMSCs).

The SNP was prepared to detect its physical characteristics including particle size, zeta potential, morphology, encapsulation efficiency and drug loading.SNP-SonoVue was constructed to detect the sustained release situation of SNP and SNP-SonoVue after low frequency ultrasound (LIFU) irradiation, and the connection of SNP-SonoVue was observed by fluorescence microscope. Effects of SNP-SonoVue on migration of BMSCs were detected to evaluate its bioactivity. BMSCs were divided into 6 groups , including Group A: SDF-1α+ 1% serum medium; Group B: SNP-SonoVue+ 1% serum culture medium; Group C: SNP-SonoVue+ 1% serum culture medium+ LIFU (1 MHz, 0.5 W/cm^2, expose 30 s stop 30 s, 4 min); Group D: BNP-SonoVue+ 1% serum medium; Group E: BNP-SonoVue+ 1% serum medium+ LIFU (1 MHz, 0.5 W/cm^2, expose 30 s stop 30 s, 4 min), Group F: PBS+ 1% serum culture medium (control group). Its tracing abilitie were investigated in vitro.

The average particle size of SNP was (220.4±9.9)nm, and the particle dispersion index (PDI) was (0.172±0.015), the average zeta potential was (35.6±1.7)mv. It was showed spherical dispersion by transmission electron microscopy. The encapsulation efficiency was up to 96.7% and the drug entrapment content was 481.76 ng/mg. Flow cytometric showed the suitable conditions for SNP-SonoVue preparation was that the ratio of SNP quality(mg) to SonoVue microbubbles number(a) was 20: (2.8×10⁹)to 40: (2.8×10⁹). Fluorescence microscopy showed that shells of SonoVue microbubbles connected with large numbers of SNP labeled with red fluorescent DiI. Drug release experiment showed that the cumulative SDF-1α release amount of SNP and SNP-SonoVue exposed to LIFU respectively were (68.61±3.97)% and (63.21±5.68)% in vitro within 7 days, and the difference was not statistically significant (P>0.05). Cell migration experiments confirmed that the transfer function of BMSCs in Group A, Ggroup B and group C was significantly higher than that in control group (P<0.05), but there was no significant difference among the Group A, Ggroup B and group C (P>0.05). In vitro development experiment showed that the SNP-SonoVue complex had obviously enhanced development effect.

SNP-SonoVue complex is successfully prepared. It has obviously enhanced development effect and can lead to migration of BMSCs.

Ultrasonic therapy; Lipid nanoparticles; Microbubbles; Stromal cell-derived factor-1alpha; Bone marrow mesenchymal stem cells; Drug tracing