Monoamine neurotransmitter functionalized poly(amidoamine) dendrimers for targeting of cabazitaxel to human prostate cancer cells

Prostate cancer ranks as the second most prevalent solid malignancy in men. Androgen deprivation therapy is a common approach of treating metastatic prostate cancer. However, development of castrate resistance in patients over the course of treatment, non-specific drug distribution and low solubility of drugs are major challenges in the treatment of prostate cancer treatment. In this study, serotonin (ST), a monoamine neurotransmitter, was explored for the site-specific delivery of cabazitaxel (CBZ) to 5HT (5-hydroxytryptamine) receptors overexpressing prostate cancer cells. ST was conjugated to G4 PAMAM dendrimers (DEND) which have well defined, highly branched, nanoscale, multifunctional architecture to carry and enhance the solubility of hydrophobic drugs. This study demonstrates the successful synthesis, characterisation, and CBZ delivery using serotonin-polyethylene glycol-dendrimer complex (ST-PEG-DEND) to DU154 human prostate cancer cells. According to the findings, CBZ@PEG-DEND showed significantly higher time- and dose-dependent cytotoxicities and growth-inhibitory effects to DU145 cells in comparison to pure CBZ. Further, the cellular uptake studies revealed high cellular uptake of targeted and fluorescent conjugate (Rho@ST-PEG-DEND) in comparison to non-targeted fluorescent conjugate (Rho@PEG-DEND), highlighting the role of ST in improved delivery of CBZ to 5HT receptor overexpressed cancer cells.