Using ultrasound-targeted microbubble destruction to enhance radiotherapy of glioblastoma

Abstract

Objective To investigate the efficacy and mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with radiotherapy (XRT) on glioblastoma. Methods The enhanced radiosensitization by UTMD was assessed through colony formation and cell apoptosis in Human glioblastoma cells (U87MG). Subcutaneous transplantation tumors in 24 nude mice implanted with U87MG cells were randomly assigned to 4 different treatment groups (Control, UTMD, XRT, and UTMD + XRT) based on tumor sizes (100–300 mm3). Tumor growth was observed for 10 days after treatment, and then histopathology stains (HE, CD34, and γH2AX) were applied to the tumor samples. A TUNEL staining experiment was applied to detect the apoptosis rate of mice tumor samples. Meanwhile, tissue proteins were extracted from animal specimens, and the expressions of dsDNA break repair-related proteins from animal specimens were examined by the western blot. Results When the radiotherapy dose was 4 Gy, the colony formation rate of U87MG cells in the UTMD + XRT group was 32 ± 8%, lower than the XRT group (54 ± 14%, p < 0.01). The early apoptotic rate of the UTMD + XRT group was 21.1 ± 3% at 48 h, higher than that of the XRT group (15.2 ± 4%). The tumor growth curve indicated that the tumor growth was inhibited in the UTMD + XRT group compared with other groups during 10 days of observation. In TUNEL experiment, the apoptotic cells of the UTMD + XRT group were higher than that of the XRT group (p < 0.05). The UTMD + XRT group had the lowest MVD value, but was not significantly different from other groups (p > 0.05). In addition, γH2AX increased due to the addition of UTMD to radiotherapy compared to XRT in immunohistochemistry (p < 0.05). Conclusions Our study clearly demonstrated the enhanced destructive effect of UTMD combined with 4 Gy radiotherapy on glioblastoma. This could be partly achieved by the increased ability of DNA damage of tumor cells.

Ultrasound stimulated microbubbles cavitation enhanced the therapeutic effect of colchicine in rats with acute gouty arthritis

“…The momentary formation of minute perforations on the cell membrane surface enhances the permeability of the cell membrane, thus improving the e ciency of delivering plasmids or drugs. Furthermore, the tremendous energy unleashed by transient cavitation is capable of obliterating microvessels within tumor tissues, rendering it a subject of keen interest in the realm of gene therapy and tumor treatment 11,12 . In this research, the application of adjusted ultrasonic parameters, such as MI and repetitive pulse frequency, allowed for the generation of low-energy steady-state cavitation.…”

Ultrasound-triggered microbubble destruction enhances the radiosensitivity of glioblastoma by inhibiting PGRMC1-mediated autophagy in vitro and in vivo

“…However, relevant studies about the effect of UTMD on the radiotherapy response of glioma are currently rare. In 2021, Peng et al [ 30 ] first confirmed that UTMD improves the destructive effect of IR on glioblastoma in a subcutaneous tumor model in nude mice, which demands to be further validated in an animal model in situ that can recapitulate various aspects of disease more accurately. Accordingly, in the present study, we established an orthotopic mouse glioblastoma model and found, for the first time, that UTMD markedly enhanced the radiosensitivity and prolonged the survival of orthotopic glioblastoma-bearing mice.…”

“…In the current study, UTMD was performed as described before with some modifications [ 30 ]. As shown in Additional file 1 : Fig.…”

Ultrasound-stimulated microbubbles enhances radiosensitivity of ovarian cancer

“…The SonoVue™ (Bracco, Milan, Italy) microbubbles encapsulating sulfur hexafluoride gas (SF6) were made following the manufacturer's recommendations (18). Before ultrasound treatment, 500 μL of freshly made microbubbles were mixed with medium (0.01%, v/v) and inverted for several minutes to allow the microbubbles to have a close touch with cells.…”

“…After 3% (v/v) microbubbles were added, cells were immediately treated with the 1-MHz probe for 1 min under the condition of duty cycle of 20% and peak negative pressure of 0.3 w/cm 2 . Next, the cells were incubated for 24 h. Subsequently, cells were irradiated using an irradiation cabinet (Primus, Siemens, Germany) at a dose of 5 or 10 Gy at a dose rate of 300 cGy/min and an energy of 6 MV (18). Afterwards, cells were used for the following MTT and colony-formation assays as well as western blot and flow cytometry analyses.…”