title: Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.
abstract: Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1α siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1α siRNA nanoparticles effectively reduced HIF1α 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 HIF1α expression in tumor tissues. When combined with photodynamic therapy, HIF1α siRNA nanoparticles enhanced the regression in tumor size resulting in a ~40% decrease in volume after 10 days. Combination therapy was found to be substantially more effective than either HIF1α 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 HIF1α siRNA into tumors as part of combination therapy along with PDT in the treatment of oral squamous cell carcinoma.
authors.affiliation: Graduate Program of Nanotechnology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Graduate Program of Bioscience Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC.
authors.forename: Rumwald Leo G
authors.initials: RL
authors.lastname: Lecaros
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Tseng
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC; Center of Biomedical Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC.
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC; Center of Biomedical Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC; Center for Nanotechnology, Chung Yuan Christian University, Taoyuan 32023, Taiwan, ROC. Electronic address: ivyhsu@cycu.edu.tw.
authors.forename: Yih-Chih
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053758:Nanoparticles; D010778:Photochemotherapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D017480:Receptors, sigma
keywords: Drug delivery; Gene silencing; Gene therapy; Nanoparticle; Photodynamic therapy