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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Chen, Yamei Liu, Xuwei Sun, Yang Liu, Keying Ding, Ding Song, Shaoli Tan, Weihong |
| Abstract | Recent advancements in antibody-drug conjugates (ADCs) targeting trophoblast surface cell antigen 2 (Trop-2) have brought important progress in the field of targeted therapy. This progress also holds promise for the treatment of small cell lung cancer (SCLC) as anti-Trop-2 therapy appears to have a safe and effective clinical activity in metastatic SCLC patients. However, effective treatments of anti-Trop-2 ADCs rely on the comprehensive assessment of Trop-2 expression at the tumor sites, SCLC exhibits intratumoral heterogeneity, making the accurate acquisition of histological biopsies a challenge. To address this issue, we herein report the development of an anti-Trop-2 aptamer consisting of 76 bases is specifically bind to Trop-2-overexpressing SCLC cells. Further truncated anti-Trop-2 aptamer with 46 nucleotides also possesses excellent in vitro and in vivo binding affinity with Trop-2 antigens. After radiolabeling with gallium-68 radionuclide, an aptamer-based molecular imaging probe was successfully fabricated named [68Ga]Ga-NOTA-TRP-c. This imaging probe demonstrated effective and precise differentiation of Trop-2-positive tumors in both murine- and human-derived animal models, exhibiting favorable metabolic profiles. Furthermore, Trop-2-positive SCLC tumors recognized by anti-Trop-2 aptamer can be treated with anti-Trop-2 ADC sacituzumab govitecan (SG), either in vitro or in vivo. Importantly, SG induces DNA damage and cell apoptosis without affecting the expression of Trop-2 on the cell surface, which makes it possible to use anti-Trop-2 aptamer to monitor the expression of Trop-2 in SCLC. This study highlights the potential of aptamer-based molecular imaging and imaging-guided SG treatment as a promising option for targeted therapy in SCLC. Graphical Abstract |
| Related Links | https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-025-03184-6.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14773155 |
| DOI | 10.1186/s12951-025-03184-6 |
| Journal | Journal of Nanobiotechnology |
| Issue Number | 1 |
| Volume Number | 23 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-03-06 |
| Access Restriction | Open |
| Subject Keyword | Biotechnology Nanotechnology Molecular Medicine Small cell lung cancer Trop-2 Aptamer Molecular imaging Antibody-drug conjugates |
| Content Type | Text |
| Resource Type | Article |
| Subject | Bioengineering Pharmaceutical Science Medicine Applied Microbiology and Biotechnology Biomedical Engineering Molecular Medicine Nanoscience and Nanotechnology |
| Journal Impact Factor | 10.6/2023 |
| 5-Year Journal Impact Factor | 11.4/2023 |
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