Fig. 5. Deep-tissue therapy of tumor models using SPINs.
a Schematic of sono-immunotherapy of subcutaneous pancreatic mouse tumors covered with 5-cm tissue. b, c Relative tumor volumes of primary (b) and distant (c) tumors of Panc02 tumor-bearing C57BL/6 mice (n = 5) after systemic injection of saline, free-drug mixture (on day 0, 3, and 6, 4 mg/kg body weight for NLG919 and aPD-L1), SPIN0 or SPIND2 (0.2 mL, 0.6 mg/mL) with or without US irradiation (1.0 MHz, 1.2 W/cm2, 50% duty cycle, 10 min). The primary tumors were covered with 5-cm tissue under US irradiation. SPIND2 + US versus SPIN0 + US: P < 0.0001 for primary tumors (b); SPIND2 + US versus SPIN0 + US: P < 0.0001 for distant tumors (c). d Survival curves of Panc02 tumor-bearing C57BL/6 mice (n = 10) after different treatments for 60 days. e Schematic of US-mediated deep-tissue sonodynamic therapy of orthotopic pancreatic rabbit tumors. f Radiolabeling stability of 131I-SPIN0 after storage in saline or 50% serum at 37 °C for different time (n = 3). g, h SPECT imaging (g) and signal intensity (h) of orthotopic pancreatic rabbit tumors after systemic injection of 131I-SPIN0 (1.0 mL, 1.5 mg/mL) for different time (n = 4). The white dotted circle indicated tumors. i Computed tomography (CT) imaging of orthotopic pancreatic rabbit tumors after systemic injection of saline or SPIN0 (1.0 mL, 1.5 mg/mL) with or without US irradiation (1.0 MHz, 1.2 W/cm2, 50% duty cycle, 30 min). The white dotted circle indicated tumors. j Tumor volume of orthotopic pancreatic rabbit tumors (n = 3) after treatments as indicated for different days. Saline + US versus SPIN0 + US: P = 0.0108. k H&E staining images of orthotopic pancreatic rabbit tumors after different treatments. The experiment was repeated independently three times with similar results. l Survival curves of orthotopic pancreatic tumor-bearing rabbits (n = 4) after different treatments for 20 days. Data are presented as mean values ± SD. Statistical significance was calculated via two-tailed Student’s t test; *P < 0.05, ***P < 0.001. Source data are provided as a Source Data file.