Multifunctional Gold Nanorod-Based Drug/SiRNA Nanocarriers for Targeted Neuroendocrine Cancer Therapy

Y. Xiao, R. Jaskula-Sztulb, H. Chen, S. Gong
University of Wisconsin-Madison, US

Keywords: nanomedicine, gold nanocarriers, siRNA delivery, somatostatin receptors

Summary:

Gastrointestinal (GI) carcinoids are neuroendocrine (NE) tumors that secrete hormones causing carcinoid syndrome. Carcinoids are often metastatic at the time of diagnosis, thus no longer amenable to curative surgery. siRNA-mediated gene silencing combined with targeted chemotherapy may be a potential therapeutic strategy for patients with carcinoid neoplasms. We have developed a gold nanorod (Au NR)-based nanocarrier conjugated with an anticancer drug (doxorubicin (DOX)) and also complexed with small interfering RNA (siRNA against ASCL1), which can specifically target the NE cancer cells with overexpressed somatostatin receptors (SSTRs) using octreotide (Oct) as an active tumor-targeting ligand. We demonstrated that the presence of the active targeting ligand Oct increased the cellular uptake of the NPs (Au-DOX-Oct) substantially in a BON cell line compared to the non-targeted NPs (Au-DOX). Additionally, the targeting ligand sped up the intracellular transport, making these NPs more efficient in delivering DOX to the nuclei of cancer cells. Au-DOX-Oct-ASCL1 siRNA was the most efficient nanocarrier in altering the neuroendocrine phenotype of BON cells and showed the strongest anti-proliferative effect. Thus, targeted delivery of anticancer drug (DOX) and genetic material (ASCL1siRNA) to NE tumor tissues can significantly enhance the therapeutic outcomes in carcinoid cancer treatment.