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Thursday, 04 June 2020 11:05

CendR peptide for Tenascin-C C domain isoform targeting.

Systemic PL3-NWs accumulate in solid tumors. The U87-MG glioblastoma mice were systemically injected with PL3-NWs or control-NWs. Five h later, the animals were intracardially perfused with DMEM/BSA and the tumors and control organs were snap-frozen, sectioned, immunoassay with rabbit anti-FAM (green), rat anti-CD31 (red) antibodies, counterstained with DAPI (blue) and imaged by confocal microscopy. Arrows point to PL3-NWs in the CD31-positive vessels, and arrowheads point to extravasated PL3-NWs in the tumor parenchyma. Author: Prakash Lingasamy Systemic PL3-NWs accumulate in solid tumors. The U87-MG glioblastoma mice were systemically injected with PL3-NWs or control-NWs. Five h later, the animals were intracardially perfused with DMEM/BSA and the tumors and control organs were snap-frozen, sectioned, immunoassay with rabbit anti-FAM (green), rat anti-CD31 (red) antibodies, counterstained with DAPI (blue) and imaged by confocal microscopy. Arrows point to PL3-NWs in the CD31-positive vessels, and arrowheads point to extravasated PL3-NWs in the tumor parenchyma. Author: Prakash Lingasamy

We describe in Scientific Reports a new homing peptide that interacts with the C-isoform of Tenascin-C (TNC-C) upregulated in malignant tissues and is capable of interacting via its C-end Rule (CendR) motif with cell-and tissue penetration receptor neuropilin-1 (NRP-1). We found that coating nanoparticles with PL3 peptide increased their tropism towards glioblastoma (GBM) and prostate carcinoma xenograft lesions in nude mice. Furthermore, treatment of glioma-bearing mice with proapoptotic PL3-guided NWs improved the survival of the mice, whereas treatment with untargeted particles had no effect. Importantly, PL3-coated nanoparticles accumulated in TNC-C and NRP-1-positive areas in clinical tumor samples, suggesting a translational relevance.

This work was performed in collaboration with the Department of Neurosurgery of Tartu University Clinics and Prof. Rolf Bjerkvig at the University of Bergen.

Lingasamy P, Tobi A, Kurm K, Kopanchuk S, Sudakov A, Salumäe M, Rätsep T,Asser T, Bjerkvig R, Teesalu T. Tumor-penetrating peptide for systemic targeting of Tenascin-C. Sci Rep. 2020 Apr 2;10(1):5809. DOI: 10.1038/s41598-020-62760-y

https://pubmed.ncbi.nlm.nih.gov/32242067

 

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