Receptor-mediated endocytosis is key in the success of targeted nanomedicines for the treatment of cancer. Various receptors have been explored for the active targeting of anticancer drugs to avoid the drawbacks of conventional anticancer drugs. This research work aimed to investigate the potential of serotonin (ST)-conjugated Vit-E nanomicelles for the targeted delivery of irinotecan hydrochloride (IRI) to human prostate cancer cells. A ST receptor-targeting conjugate was synthesized by conjugating ST and d-α-tocopheryl polyethylene glycol succinate via a two-step synthesis reaction. The developed formulation demonstrated a size of about 14 nm, a negative zeta potential of around -20 mV, a high drug encapsulation efficiency, and sustained drug release over 48 h. Cytotoxicity studies revealed that ST-conjugated, IRI-loaded nanomicelles (IRI-STNM) were not only toxic to human prostate cancer cells but also eradicate these cells present in the form of 3D spheroids. This cytotoxicity of IRI-STNM was mediated through induction of apoptosis, reactive oxygen species generation, change in mitochondrial membrane potential, and inhibition of cell migration. Further, IRI-STNM performed significantly better than the native IRI and nontargeted nanomicelles, which was led by a higher cellular uptake of IRI-STNM, indicating the role of ST in targeting of drug-loaded nanomicelles.
Keywords: 3D spheroids; human prostate cancer; irinotecan hydrochloride; serotonin; targeted nanomicelles.