Modular Nanotransporters Containing Anti-PSMA Nanobodies Are Able to Penetrate into the Nuclei of Prostate Cancer Cells

Polypeptide modular nanotransporters (MNTs) were engineered as a targeted delivery platform for prostate cancer cells. The constructs integrate a ligand module to facilitate specific cellular binding and internalization, and a nuclear localization signal (NLS) to enable subsequent nuclear translocation. Two distinct ligand modules were utilized: (a) a nanobody targeting prostate-specific membrane antigen (anti-PSMA) and (b) a gastrin-releasing peptide (GRP) fragment targeting the GRP receptor (GRPR). It was shown that all modules within MNT-antiPSMA and MNT-GRP retained their functional properties. The MNT-antiPSMA construct demonstrated the capacity to accumulate specifically in the nuclei of prostate cancer cells with both low and high PSMA expression. Conversely, MNT-GRP exhibited selective nuclear entry exclusively in cells characterized by high GRPR expression.