Can targeted nanoparticles deliver gene-silencing RNA into tumors and slow their growth in a xenograft model?

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Researchers developed a self-assembled nanoparticle (NP) to efficiently deliver small interfering RNA (siRNA) to tumors by intravenous (IV) administration. In this experimental xenograft-model study, the nanoparticles were made by mixing carrier DNA, siRNA, protamine, and lipids, then modifying them with polyethylene glycol and the ligand anisamide.

Four hours after IV injection into a xenograft model, tumor accumulation was reported as 70–80% of injected siRNA/g; approximately 10% was detected in the liver and approximately 20% was recovered in the lung. Confocal microscopy showed that the targeted nanoparticles efficiently delivered fluorescent-labeled siRNA into the cytoplasm of the sigma receptor-expressing NCI-H460 xenograft tumor, whereas free siRNA and non-targeted nanoparticles showed little uptake.

Three daily injections of siRNA formulated in the targeted nanoparticles, at 1.2 mg/kg, silenced epidermal growth factor receptor (EGFR) in the tumor and induced apoptosis in approximately 15% of tumor cells. Treatment with targeted nanoparticles achieved 40% tumor growth inhibition; when combined with cisplatin, complete tumor growth inhibition lasted for 1 week.

Serum liver enzyme levels and body weight monitoring during treatment indicated a low level of toxicity of the formulation. The carrier itself also showed little immunotoxicity (IMT).