Ultrasound-mediated drug-free theranostics for treatment of prostate cancer
Issued Date
2024-05-01
Resource Type
ISSN
2452199X
Scopus ID
2-s2.0-85183552504
Journal Title
Bioactive Materials
Volume
35
Start Page
45
End Page
55
Rights Holder(s)
SCOPUS
Bibliographic Citation
Bioactive Materials Vol.35 (2024) , 45-55
Suggested Citation
Perera R.H., Berg F.M., Abenojar E.C., Nittayacharn P., Kim Y., Wang X., Basilion J.P., Exner A. Ultrasound-mediated drug-free theranostics for treatment of prostate cancer. Bioactive Materials Vol.35 (2024) , 45-55. 55. doi:10.1016/j.bioactmat.2023.12.012 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95590
Title
Ultrasound-mediated drug-free theranostics for treatment of prostate cancer
Corresponding Author(s)
Other Contributor(s)
Abstract
Lipid-shelled nanobubbles (NBs) can be visualized and activated using noninvasive ultrasound (US) stimulation, leading to significant bioeffects. Prior work demonstrates that active targeting of NBs to prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer (PCa) results in enhanced cellular internalization and prolongs NB retention with persistent, cancer-cell specific acoustic activity. In this work, we hypothesized that tumor-accumulated PSMA-NBs combined with low frequency unfocused therapeutic US (TUS) will lead to selective damage and induce a specific therapeutic effect in PSMA-expressing tumors compared to PSMA-negative tumors. We observed that the internalized NBs and cellular compartments were disrupted after the PSMA-NB + TUS (targeted NB therapy or TNT) application, yet treated cells remained intact and viable. In vivo, PSMA-expressing tumors in mice receiving TNT treatment demonstrated a significantly greater extent of apoptosis (78.4 ± 9.3 %, p < 0.01) compared to controls. TNT treatment significantly inhibited the PSMA expressing tumor growth and increased median survival time by 103 %, p < 0.001). A significant reduction in tumor progression compared to untreated control was also seen in an orthotopic rabbit PCa model. Results demonstrate that cavitation of PSMA-NBs internalized via receptor-mediated endocytosis into target PCa cells using unfocused ultrasound results in significant, tumor-specific bioeffects. The effects, while not lethal to PSMA-expressing cancer cells in vitro, result in significant in vivo reduction in tumor progression in two models of PCa. While the mechanism of action of these effects is yet unclear, it is likely related to a locally-induced immune response, opening the door to future investigations in this area.