Objective To prepare a new type of lipid nanoprobes (HD@P-NPs), investigate their in vitro ultrasound imaging effects, and observe their migration inhibition of keloid fibroblasts as well as their therapeutic efficacy in cascade amplification. Methods In this study, solid lipid nanocomposites were used as drug carriers, core-loaded with perfluorohexane (PFH), and piggybacked with hematoporphyrin monomethyl ether (HMME) and Doxorubicin(DOX), and ultrasonic emulsification was used to prepare HD@P-NPs nano-probes, to observe the microscopic morphology of the nano-probes and to detect their particle sizes, potentials, PDI dispersion, and stability, and to calculate the encapsulation rate of the corresponding drug and drug-loading rate, and to explore the effect of ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) on the imaging of HD@P-NPs in the presence of LIFU; logarithmically grown keloid fibroblasts KFS were taken and co-cultured with different experimental groups and divided into the following five groups: control, LIFU irradiation alone, D@P-NPs, HD@P-NPs, and HD@P-NPs+LIFU irradiation, and the acoustic kinetic efficacy of the nanoprobe HD@P-NPs was assessed using Calcein-AM/propidium iodide staining method, cell viability was detected by MTT assay, and the migration ability of KFS cells was studied and DCFH-DA indicator was applied to observe intracellular reactive oxygen species production. RESULTS ①The nanoprobes HD@P-NPs were prepared with uniform size and good stability, with an average particle size of 170.36±6.03nm, a potential of -36.91±3.56mv, and HMME encapsulation and drug loading rates of 67.41% and 5.18%, respectively, and DOX encapsulation and drug loading rates of 72.80% and 11.20%, respectively.②After LIFU irradiation, the phase transition of lipid nanoprobes HD@P-NPs produces microbubbles, and the maximum imaging effect can be achieved at 3W/cm2 and 2min.③MTT and Calcein-AM/propidium iodide staining showed that the nanoprobe HD@P-NPs had a significant cytostatic effect on KFS cells under combined LIFU conditions, which showed a clear red fluorescence, while LIFU irradiation alone did not show any cytostatic effect, the cytostatic effect was weaker in the D@P-NPs group and the HD@P-NPs group than in the HD@P-NPs+LIFU group, and there was no statistically significant difference in cytostatic inhibition between the two groups (P > 0.05). ④KFS cell migration assay showed that there was no statistically significant difference in cell migration inhibition between the D@P-NPs group and the HD@P-NPs group in the absence of LIFU (P＞0.05), while the HD@P-NPs+LIFU group showed the maximum cell migration inhibition, with a migration rate of only 10.32% (P < 0.05), and a significant increase of ROS production of the KFS cells in the presence of LIFU. Conclusion Lipid nanoprobes HD@P-NPs were successfully prepared, which can increase the effective drug concentration in the target area under the combined LIFU effect and realize the acoustic power cascade amplification therapy of KFS cells under ultrasound visualization.