PSMA-targeted SMART molecules outfitted with SN38

Savoy, Emily A.; Olatunji, Feyisola P.; Mesbahi, Nooshin; Ballard, Ryanne K.; Lovingier, Christine L.; Hendricksen, Aaron T.; Fulton, Melody D.; Berkman, Clifford E.

doi:10.1016/j.bmcl.2024.129657

Bioorganic & Medicinal Chemistry Letters

2024

DOI: 10.1016/j.bmcl.2024.129657

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PSMA-targeted SMART molecules outfitted with SN38

Emily A. Savoy,

Feyisola P. Olatunji,

Nooshin Mesbahi

et al.

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2024

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PSMA-Targeted 2-Deoxyglucose-Based Dendrimer Nanomedicine for the Treatment of Prostate Cancer

Rani,

Pulukuri,

Wei

et al. 2024

Biomacromolecules

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Prostate cancer (PC) is the fifth leading cause of cancer-related deaths among men worldwide. Prostate-specific membrane antigen (PSMA), a molecular target of PC, is clinically used for the treatment and diagnosis of PC using radioligand approaches. However, no PSMA-based chemotherapies have yet been approved by the FDA. Here, we present a novel therapeutic approach using PSMA-targeted 2deoxyglucose-dendrimer (PSMA-2DG-D) for targeted delivery of a potent tyrosine kinase inhibitor, cabozantinib (Cabo), selectively to PC cells. PSMA-2DG-D demonstrates intracellular localization in PSMA (+) PC cells through PSMA-mediated internalization. This PSMA-specific targeting translates to enhanced efficacy of Cabo compared to the free drug when conjugated to PSMA-2DG-D. Furthermore, systemically administered fluorescently labeled PSMA-2DG-D-Cy5 specifically targets PSMA (+) tumors with minimal off-target accumulation in the PC3-PIP tumor xenograft mouse model. This demonstrates that the PSMA-2DG-D platform is a promising new delivery system for potent chemotherapeutics, where systemic side effects are a significant concern.

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PSMA-Targeted 2-Deoxyglucose-Based Dendrimer Nanomedicine for the Treatment of Prostate Cancer

Rani,

Pulukuri,

Wei

et al. 2024

Biomacromolecules

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show abstract

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PSMA-targeted SMART molecules outfitted with SN38

Cited by 1 publication

References 58 publications

PSMA-Targeted 2-Deoxyglucose-Based Dendrimer Nanomedicine for the Treatment of Prostate Cancer

PSMA-Targeted 2-Deoxyglucose-Based Dendrimer Nanomedicine for the Treatment of Prostate Cancer

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