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Optimized Anti–Prostate‐Specific Membrane Antigen Single‐Chain Variable Fragment–Loaded Nanobubbles as a Novel Targeted Ultrasound Contrast Agent for the Diagnosis of Prostate Cancer
Author(s) -
Ding Yu,
Cao Qifeng,
Qian Subo,
Chen Xiaolong,
Xu Yuhong,
Chen Jian,
Shen Haibo
Publication year - 2020
Publication title -
journal of ultrasound in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 91
eISSN - 1550-9613
pISSN - 0278-4297
DOI - 10.1002/jum.15155
Subject(s) - lncap , glutamate carboxypeptidase ii , prostate cancer , flow cytometry , cancer research , in vivo , medicine , in vitro , immunofluorescence , antigen , microbiology and biotechnology , cancer , antibody , chemistry , immunology , biology , biochemistry
Objectives To prepare optimized prostate‐specific membrane antigen (PSMA) single‐chain variable fragment (scFv)–loaded nanobubbles (NBs) as a novel targeted ultrasound (US) contrast agent for diagnosis and treatment of prostate cancer (PCa). Methods Prostate‐specific membrane antigen scFv‐loaded NBs were prepared by membrane hydration and biotin‐streptavidin conjugation. Flow cytometry was used to observe the binding rate of the targeted NBs to PSMA‐expressing cells. Contrast‐enhanced US was used to monitor targeted and nontargeted NBs administered to nude mice with 22RV1, LNCaP, and PC‐3 xenograft tumors. The specific binding ability of the targeted NBs was further examined by fluorescence imaging of tumor cryosections. Results Uniformly sized targeted NBs were successfully prepared (mean ± SD, 485.3 ± 28.4 nm). The NBs showed good stability and bound specifically to LNCaP and 22RV1 cells with high PSMA expression in vitro but did not bind to PC‐3 cells without PSMA expression. The targeted NBs presented good US enhancement, and the results of the in vivo xenograft tumor nude mouse model showed that the peak contrast intensity in LNCaP and 22RV1 cells was significantly higher for the targeted NBs than the nontargeted NBs ( P < .05), whereas there was no significant difference in PC‐3 cells. Immunofluorescence results obtained from tumor sections confirmed that the targeted NBs were capable of targeting PSMA‐expressing tumor cells. Conclusions These novel PSMA scFv‐loaded NBs have proven to be an excellent US contrast agent for imaging PSMA‐expressing PCa and have the potential to not only enable efficient and safe molecular imaging but also to serve as a delivery system for targeted PCa therapies.