Nanoparticle delivery of HIF1 alpha siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer

作者：Chen Wei Hua; Lecaros Rumwald Leo G; Tseng Yu Cheng; Huang Leaf; Hsu Yih Chih^*

来源：Cancer Letters, 2015, 359(1): 65-74.

DOI：10.1016/j.canlet.2014.12.052

• Gene therapy
• Drug delivery
• Nanoparticle
• Gene silencing
• Photodynamic therapy

Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1 alpha siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1 alpha siRNA nanoparticles effectively reduced HIF1 alpha expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Intravenous injection of the same nanoparticles into human SCC4 or SAS xenografted mice likewise resulted in concentrated siRNA accumulation and reduced HIF1 alpha expression in tumor tissues. When combined with photodynamic therapy, HIF1 alpha siRNA nanoparticles enhanced the regression in tumor size resulting in a similar to 40% decrease in volume after 10 days. Combination therapy was found to be substantially more effective than either HIF1 alpha siRNA or photodynamic therapy alone. Results from caspase-3, TUNEL, and CD31 marker studies support this conclusion. Our results show the potential use of LCP nanoparticles for efficient delivery of HIF1 alpha siRNA into tumors as part of combination therapy along with PDT in the treatment of oral squamous cell carcinoma.

• 出版日期2015-4-1