title: In vivo Biocompatibility, Biodistribution and Therapeutic Efficiency of Titania Coated Upconversion Nanoparticles for Photodynamic Therapy of Solid Oral Cancers.
abstract: Despite the advantages of using photodynamic therapy (PDT) for the treatment of head and neck tumors, it can only be used to treat early stage flat lesions due to the limited tissue penetration ability of the visible light. Here, we developed near-infrared (NIR) excitable upconversion nanoparticle (UCN) based PDT agent that can specifically target epithelial growth factor receptor (EGFR) overexpressing oral cancer cells, in a bid to widen the application of PDT against thick and solid advanced or recurrent head and neck cancers. In vivo studies using the synthesized anti-EGFR-PEG-TiO2-UCNs following systemic administration displayed no major sub-acute or long term toxic effects in terms of blood biochemical, hematological or histopathological changes at a concentration of 50 mg/kg. NIR-PDT even in the presence of a 10 mm tissue phantom placed over the xenograft tumor, showed significant delay in tumor growth and improved survival rate compared to conventional chlorin-e6 (Ce6) PDT using 665 nm red light. Our work, one of the longest study till date in terms of safety (120 d), PDT efficacy (35 d) and survival (60 d), demonstrates the usefulness of UCN based PDT technology for targeted treatment of thick and bulky head and neck tumors.
authors: NUS Graduate School for Integrative Sciences & Engineering (NGS), Singapore 117456.; Department of Biomedical Engineering, National University of Singapore, Singapore 117575.
authors: Sasidharan Swarnalatha
authors: SS
authors: Lucky
authors: Department of Biomedical Engineering, National University of Singapore, Singapore 117575.
authors: Niagara Muhammad
authors: NM
authors: Idris
authors: Department of Biomedical Engineering, National University of Singapore, Singapore 117575.
authors: Kai
authors: K
authors: Huang
authors: Department of Biomedical Engineering, National University of Singapore, Singapore 117575.
authors: Jaejung
authors: J
authors: Kim
authors: Institute of Physical Chemistry, Zhejiang Normal University, P. R. China 321004.
authors: Zhengquan
authors: Z
authors: Li
authors: Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610.
authors: Patricia Soo Ping
authors: PS
authors: Thong
authors: School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore 637459.
authors: Rong
authors: R
authors: Xu
authors: Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610.
authors: Khee Chee
authors: KC
authors: Soo
authors: NUS Graduate School for Integrative Sciences & Engineering (NGS), Singapore 117456.; Department of Biomedical Engineering, National University of Singapore, Singapore 117575.
authors: Yong
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007259:Infrared Rays; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism / Q000628:therapy*; D053758:Nanoparticles / Q000528:radiation effects / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001672:Biocompatible Materials; D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C009495:titanium dioxide; C062985:phytochlorin; D014025:Titanium; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Oral cancer; near-infrared.; photodynamic therapy; titanium dioxide; upconversion nanoparticles