title: Nanoparticle Delivered VEGF-A siRNA Enhances Photodynamic Therapy for Head and Neck Cancer Treatment.
abstract: Photodynamic therapy (PDT) is believed to promote hypoxic conditions to tumor cells leading to overexpression of angiogenic markers such as vascular endothelial growth factor (VEGF). In this study, PDT was combined with lipid-calcium-phosphate nanoparticles (LCP NPs) to deliver VEGF-A small interfering RNA (siVEGF-A) to human head and neck squamous cell carcinoma (HNSCC) xenograft models. VEGF-A were significantly decreased for groups treated with siVEGF-A in human oral squamous cancer cell (HOSCC), SCC4 and SAS models. Cleaved caspase-3 and in situ TdT-mediated dUTP nick-end labeling assay showed more apoptotic cells and reduced Ki-67 expression for treated groups compared to phosphate buffered saline (PBS) group. Indeed, the combined therapy showed significant tumor volume decrease to ~70 and ~120% in SCC4 and SAS models as compared with untreated PBS group, respectively. In vivo toxicity study suggests no toxicity of such LCP NP delivered siVEGF-A. In summary, results suggest that PDT combined with targeted VEGF-A gene therapy could be a potential therapeutic modality to achieve enhanced therapeutic outcome for HNSCC.
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.
authors.forename: Rumwald Leo G
authors.initials: RL
authors.lastname: Lecaros
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.|Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Center for Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.
authors.forename: Tsai-Chia
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.|Center for Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.|Center of Biomedical Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.
authors.forename: Yih-Chih
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010778:Photochemotherapy; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D053148:Caspase 3