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Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles.
- Source :
-
Journal of materials chemistry. B [J Mater Chem B] 2024 Feb 28; Vol. 12 (9), pp. 2324-2333. Date of Electronic Publication: 2024 Feb 28. - Publication Year :
- 2024
-
Abstract
- Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans -cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo , with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC.
Details
- Language :
- English
- ISSN :
- 2050-7518
- Volume :
- 12
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of materials chemistry. B
- Publication Type :
- Academic Journal
- Accession number :
- 38324337
- Full Text :
- https://doi.org/10.1039/d3tb02543h