Low-intensity histotripsy based on acoustically-responsive scaffolds for tumor mechanical destruction and immune responses

Background Mechanical ablation enables precise, non-thermal tissue destruction with rapid necrosis clearance and mass-effect decompression. However, high-intensity histotripsy is limited by restricted targeting depth and high cost.Methods We introduced an acoustically responsive scaffold (ARS)–based low-intensity histotripsy (LIH) approach for tumor mechanical disruption and evaluated its ablative efficacy and immunomodulatory potential. In total, 25 New Zealand white rabbits bearing VX2 tumors were randomly assigned to the control, ARS, LIH1 (pulse repetition frequency (PRF) = 20 Hz, pulse length (PL) = 5.37 ms + ARS), LIH2 (PRF = 20 Hz, PL = 3.36 ms + ARS), and LIH3 (PRF = 38 Hz, PL = 5.37 ms + ARS) groups (n = 5 each).Results Compared with LIH2 and LIH3, LIH1 produced greater tumor damage area (31.83 ± 15.11 mm2) and damage area ratio (20.90 ± 7.07%), although differences were not statistically significant. All LIH groups exhibited significantly greater tissue damage than the ARS (0.00052 ± 0.00055 mm2; 0.0005 ± 0.00054%) and control (0.00 ± 0.00 mm2; 0.00 ± 0.00%) groups. LIH treatment significantly inhibited tumor growth (p < 0.05). Immunofluorescence analysis demonstrated increased CD8 and CD11c expression in tumor tissues following LIH (p < 0.05).Conclusions These findings indicate that LIH effectively induces mechanical tumor disruption and enhances antitumor immune responses.