Microbubbles Ultrasonic Cavitation Regulates Tumor Interstitial Fluid Pressure and Enhances Sonodynamic Therapy

Abstract

Sonodynamic therapy (SDT) is a promising treatment method for solid tumors. However, the high interstitial fluid pressure (IFP) in tumor tissues limits the accumulation of sonosensitizers. In the present study, microbubbles ultrasonic cavitation was used to regulate the tumor’s IFP and evaluate SDT effects. Rabbit VX2 tumor tissues were treated with microbubbles ultrasonic cavitation. The IFP of different tumor parts before and after cavitation was measured by the WIN method. The accumulation of the sonosensitizers hematoporphyrin monomethyl ether (HMME) in tumor tissues was observed using an ultramicro spectrophotometer and laser confocal microscope. Then, tumor-bearing rabbits were treated with SDT once a week for eight weeks and the therapeutic effect was evaluated. After microbubbles ultrasonic cavitation treatment, the tumor’s IFP decreased and the HMME concentration increased. We concluded that microbubbles ultrasonic cavitation can increase HMME accumulation in rabbit VX2 tumors and increase SDT therapeutic effects.

Tumor perfusion enhancement by microbubbles ultrasonic cavitation reduces tumor glycolysis metabolism and alleviate tumor acidosis

“…It also implies that ultrasonically enhanced blood flow may not promote tumor growth and metastasis. Previous study also suggested that therapeutic ultrasound with microbubbles induced perfusion enhancement does not increase tumor growth rate or metastasis in rabbit VX2 tumors, suggesting that USMC is a safe method to increase tumor perfusion ( 62 ).…”

Low-intensity focused ultrasound targeted microbubble destruction reduces tumor blood supply and sensitizes anti-PD-L1 immunotherapy

“…Attractively, UTMD can destroy tumor blood vessels in the site through cavitation to reduce adverse effects. And vascular rupture generated by disruption of micro- or nano-droplets with ultrasound can reduce IFP, break the pore size limitation between endothelial cells, and expand tissue space to facilitate drug penetration ( Ho and Yeh, 2017 ; Cao et al, 2018 ; Ho et al, 2018 ; Xi et al, 2022 ; Zheng et al, 2023 ). In light of the above theory, it is reasonable to speculate that the destruction of tumor vasculature by LIFU-TMD treatment caused incomplete vessel wall structure and decreased IFP, which could promote the penetration of anti-PD-L1 antibodies into tumors through the enlarged vascular space.…”

Recent advances in sonodynamic therapy strategies for pancreatic cancer

“…Second, SDT needs to generate sufficient amounts of ROS, and the ROS produced should effectively be able to kill tumor cells. However, the high interstitial fluid pressure in pancreatic tumors, generated by the abundant tumor stroma, presents a challenge for the successful penetration and distribution of sonosensitizers in the tumor tissue (Xi et al, 2022). In addition, the hypoxic tumor microenvironment of pancreatic tumors inhibits the generation of ROS, and the high concentration of glutathione (GSH) in pancreatic tumors can consume the ROS produced by SDT, which in turn weakens the lethality to cells (Kshattry et al, 2019; Tang et al, 2022).…”