Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
Guizhou University School of Medicine, Guiyang, Guizhou, 550025, People's Republic of China.
Int J Nanomedicine. 2021 Nov 16;16:7685-7695. doi: 10.2147/IJN.S330237. eCollection 2021.
In recent years, nuclear medicine imaging and therapy for prostate cancer have radically changed through the introduction of radiolabeled prostate-specific membrane antigen (PSMA)-binding peptides. However, these small molecular probes have some inherent limitations, including high nephrotoxicity and short circulation time, which limits their utility in biological systems.
In this study, organic melanin nanoparticles were used to directly label the long half-life radionuclide I (t=100.8 h), and PSMA small molecular groups were efficiently bonded on the surface of nanoparticles to construct the PSMA-targeted long-retention nanoprobe I-PPMN, which has the potential to increase tumor uptake and prolong residence time. The results showed that the nanoprobe could substantially aggregate in the tumors of prostate cancer xenograft mice and was visible for more than 72 h. Positron Emission Computed Tomography (PET) imaging showed that the nanoprobe could be used for precise imaging of prostate cancer with high expression of PSMA. In addition, organic melanin nanoparticles labeled with an elemental radionuclide achieved a stable, metal-free structure. Cell experiments and mouse toxicity experiments indicated that the nanoprobe has high safety.
The new nanoprobe constructed in this study has high specificity and biocompatibility. In the future, combined with the multifunctional potential of melanin nanoparticles, this nanoprobe is expected to be used in the integrated theranostics of prostate cancer.
近年来，通过引入放射性标记的前列腺特异性膜抗原（PSMA）结合肽，前列腺癌的核医学成像和治疗发生了根本性变化。然而，这些小分子探针存在一些固有局限性，包括高肾毒性和短循环时间，这限制了它们在生物系统中的应用。
在这项研究中，有机黑色素纳米粒子被用于直接标记长半衰期放射性核素 I（t=100.8 h），并在纳米粒子表面高效结合 PSMA 小分子基团，构建具有增加肿瘤摄取和延长滞留时间潜力的 PSMA 靶向长滞留纳米探针 I-PPMN。结果表明，该纳米探针可在前列腺癌异种移植小鼠的肿瘤中大量聚集，可在 72 h 以上可见。正电子发射断层扫描（PET）成像显示，该纳米探针可用于高表达 PSMA 的前列腺癌的精确成像。此外，用元素放射性核素标记的有机黑色素纳米粒子实现了稳定的、无金属的结构。细胞实验和小鼠毒性实验表明，该纳米探针具有很高的安全性。
本研究构建的新型纳米探针具有高特异性和生物相容性。在未来，结合黑色素纳米粒子的多功能潜力，该纳米探针有望用于前列腺癌的综合治疗。
