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Published on: June 12, 2021
Targeted Biosynthetic Nanobubbles for Ultrasound Molecular Imaging of Prostate Cancer
Tingting Liu1, Jieqiong Wang2, Tao Cui3
1Department of Ultrasound, The Second People's Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, China; State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Objective:
As the second leading cause of cancer-related mortality in males worldwide, prostate cancer (PCa) presents an urgent need for advanced molecular imaging strategies to improve diagnostic precision. This study presents CD147-targeted nanobody-conjugated biosynthetic gas vesicles (CD147-hGVs) as a high-performance ultrasound molecular imaging probe for precise and noninvasive diagnosis of PCa.
Methods:
Biosynthetic gas vesicles (hGVs) were site-specifically functionalized with anti-CD147 nanobodies via controlled maleimide-thiol conjugation chemistry using Mal-PEG2000-NHS heterobifunctional crosslinkers. Systematic characterization included stability assessments, in vitro targeting validation (flow cytometry, cell adhesion, and immunofluorescence on PC-3 cell lines), and in vivo ultrasound imaging in PCa-bearing nude mice using Clinical ultrasound diagnostic equipment Mindray Resona 9T.
Results:
CD147 -hGVs exhibited remarkable stability with sustained monodispersity (PDI <0.2) and consistent hydrodynamic diameter (234.4 ± 7.6 nm at day 1 vs 236.0 ± 9.8 nm at day 10, p = 0.32). In vitro targeting assays revealed about 7-fold higher binding affinity of CD147-hGVs to PC-3 cells compared to non-targeted controls (p < 0.001). In vivo molecular ultrasound imaging showed tumor-specific signal enhancement persisting for >15 min post-injection, with CD147-hGVs achieving about 6-fold higher contrast to Con-hGVs (p < 0.01).
Conclusion:
Anti-CD147 nanobody conjugated biological gas vesicles exhibit excellent stability and enhanced targeting ability for prostate cancer cells, making them a promising novel molecular probe for ultrasound imaging and potential therapy for prostate cancer.
