Anti- siRNA-Loaded Nanoparticles Block the Growth of Anaplastic Thyroid Cancer Xenograft.

The high frequency of -promoting mutations and the increased expression of mRNA in anaplastic thyroid cancer (ATC) make TERT a suitable molecular target for the treatment of this lethal neoplasm. In this study, we encapsulated an anti- oligonucleotide in biocompatible nanoparticles and analyzed the effects of this novel pharmaceutical preparation in preclinical models of ATC. Biocompatible nanoparticles were obtained in an acidified aqueous solution containing chitosan, anti- oligoRNAs, and poloxamer 188 as a stabilizer. The effects of these anti- nanoparticles (Na-siTERT) were tested on ATC cell lines (CAL-62 and 8505C) and on xenograft tumors obtained by flank injection of CAL-62 cells into SCID mice. The Na-siTERT reduced the viability and migration of CAL-62 and 8505C cells after 48-hour incubation. Intravenous administration (every 48 hours for 13 days) of this encapsulated drug in mice hosting a xenograft thyroid cancer determined a great reduction in the growth of the neoplasm (about 50% vs. untreated animals or mice receiving empty nanoparticles), and decreased levels of Ki67 associated with lower hTERT expression. Moreover, the treatment resulted in minimal invasion of nearby tissues and reduced the vascularity of the xenograft tumor. No signs of toxicity appeared following this treatment. Telomere length was not modified by the Na-siTERT, indicating that the inhibitory effects of neoplasm growth were independent from the enzymatic telomerase function. These findings demonstrate the potential suitability of this anti-TERT nanoparticle formulation as a novel tool for ATC treatment. .