Theranostics 2016; 6(11):1844-1865. doi:10.7150/thno.15088
In vivo Biocompatibility, Biodistribution and Therapeutic Efficiency of Titania Coated Upconversion Nanoparticles for Photodynamic Therapy of Solid Oral Cancers
1. NUS Graduate School for Integrative Sciences & Engineering (NGS), Singapore 117456.
2. Department of Biomedical Engineering, National University of Singapore, Singapore 117575.
3. Institute of Physical Chemistry, Zhejiang Normal University, P. R. China 321004.
4. Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610.
5. School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore 637459.
Lucky SS, Idris NM, Huang K, Kim J, Li Z, Thong PSP, Xu R, Soo KC, Zhang Y. In vivo Biocompatibility, Biodistribution and Therapeutic Efficiency of Titania Coated Upconversion Nanoparticles for Photodynamic Therapy of Solid Oral Cancers. Theranostics 2016; 6(11):1844-1865. doi:10.7150/thno.15088. Available from http://www.thno.org/v06p1844.htm
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.
Keywords: Oral cancer, EGFR, photodynamic therapy, upconversion nanoparticles, titanium dioxide, near-infrared.