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已发表论文
细胞合成靶向超声分子成像探针及其在前列腺癌诊断中的应用
Authors Li Z, Liu T, Cui T, Shen X , Liu C, Yan F
Received 4 September 2025
Accepted for publication 12 December 2025
Published 30 December 2025 Volume 2025:20 Pages 15921—15937
DOI https://doi.org/10.2147/IJN.S561230
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Xing Zhang
Zhenzhou Li,1,* Tingting Liu,1,* Tao Cui,2,* Xiong Shen,1,3 Chenxing Liu,4 Fei Yan4
1Department of Ultrasound, The Second People’s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518061, People’s Republic of China; 2Nuclear Medicine Department, Shenzhen Hezheng Hospital, Shenzhen, 518055, People’s Republic of China; 3Graduate School, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of China; 4State Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Fei Yan, Email fei.yan@siat.ac.cn
Purpose: The traditional construction of targeted ultrasound molecular imaging probes relies on multistep chemical synthesis strategies, which are time-consuming and inefficient, thereby limiting technological advancements. To address this, we developed a novel genetic engineering approach for biosynthesizing targeted nanoprobes for prostate cancer diagnosis.
Materials and Methods: The anti-PSMA nanobody-encoding gene was fused to the C-terminus of the gas vesicle structural protein gene GvpC and cloned into a pBV220 plasmid with a hyperthermia-responsive gene expression circuit. This recombinant plasmid was transformed into E. coli BL21(A1) harboring pET-28a-ΔGvpC-eGVs plasmids to create PSMA-GVs@E. coli genetically engineered bacteria. The probe assembly were involved in two-step gene expression procedure. ΔGvpC-eGVs were first induced by IPTG, followed by temperature-triggered (42°C) production of PSMA-GvpC proteins that spontaneously assembled onto GVs.
Results: The biosynthesized PSMA-eGVs probes exhibited a uniform size (100– 200 nm) and demonstrated excellent targeting capability in prostate cancer cells. In vivo studies confirmed effective tumor vascular penetration and specific binding with PSMA-positive tumor cells, resulting in significantly stronger acoustic signals than the non-targeted EGFP-eGVs controls.
Conclusion: This cellular synthesis strategy enables efficient production of targeted ultrasound molecular imaging probes through genetically engineering technology, providing a promising platform for precision cancer diagnostics.
Keywords: ultrasound molecular imaging, targeted ultrasound molecular imaging probe, prostate cancer diagnosis, gas vesicles, cellular synthesis
1Department of Ultrasound, The Second People’s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518061, People’s Republic of China; 2Nuclear Medicine Department, Shenzhen Hezheng Hospital, Shenzhen, 518055, People’s Republic of China; 3Graduate School, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of China; 4State Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Fei Yan, Email fei.yan@siat.ac.cn
Purpose: The traditional construction of targeted ultrasound molecular imaging probes relies on multistep chemical synthesis strategies, which are time-consuming and inefficient, thereby limiting technological advancements. To address this, we developed a novel genetic engineering approach for biosynthesizing targeted nanoprobes for prostate cancer diagnosis.
Materials and Methods: The anti-PSMA nanobody-encoding gene was fused to the C-terminus of the gas vesicle structural protein gene GvpC and cloned into a pBV220 plasmid with a hyperthermia-responsive gene expression circuit. This recombinant plasmid was transformed into E. coli BL21(A1) harboring pET-28a-ΔGvpC-eGVs plasmids to create PSMA-GVs@E. coli genetically engineered bacteria. The probe assembly were involved in two-step gene expression procedure. ΔGvpC-eGVs were first induced by IPTG, followed by temperature-triggered (42°C) production of PSMA-GvpC proteins that spontaneously assembled onto GVs.
Results: The biosynthesized PSMA-eGVs probes exhibited a uniform size (100– 200 nm) and demonstrated excellent targeting capability in prostate cancer cells. In vivo studies confirmed effective tumor vascular penetration and specific binding with PSMA-positive tumor cells, resulting in significantly stronger acoustic signals than the non-targeted EGFP-eGVs controls.
Conclusion: This cellular synthesis strategy enables efficient production of targeted ultrasound molecular imaging probes through genetically engineering technology, providing a promising platform for precision cancer diagnostics.
Keywords: ultrasound molecular imaging, targeted ultrasound molecular imaging probe, prostate cancer diagnosis, gas vesicles, cellular synthesis