Nanoparticle-induced intraperitoneal hyperthermia and targeted photoablation in treating ovarian cancer

// Chao-Chih Wu 1, 3 , Yuh-Cheng Yang 2 , Yun-Ting Hsu 3 , T.-C. Wu 5, 6, 7, 8 , Chien-Fu Hung 5, 6, 7, 8 , Jung-Tang Huang 1 , Chih-Long Chang 2, 3, 4 1 Graduate Institute of Mechanical and Electrical Engineering, National Taipei University of Technology, Taipei City, Taiwan 2 Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City, Taiwan 3 Department of Medical Research, Mackay Memorial Hospital, Taipei City, Taiwan 4 Department of Medicine, Mackay Medical College, Sanchi, New Taipei City, Taiwan 5 Department of Pathology, The Johns Hopkins University, Baltimore, Maryland, USA 6 Department of Oncology, The Johns Hopkins University, Baltimore, Maryland, USA 7 Department of Obstetrics and Gynecology, The Johns Hopkins University, Baltimore, Maryland, USA 8 Department of Molecular Microbiology and Immunology, The Johns Hopkins University, Baltimore, Maryland, USA Correspondence to: Chih-Long Chang, e-mail: clchang@mmc.edu.tw Jung-Tang Huang, e-mail: jthuang@ntut.edu.tw Keywords: hypethermia, gold nanoshells, ovarian cancer Received: April 23, 2015      Accepted: July 22, 2015      Published: August 03, 2015 ABSTRACT Hyperthermic intraperitoneal chemotherapy is effective in treating various intra-abdominal malignancies. However, this therapeutic modality can only be performed during surgical operations and cannot be used repeatedly. We propose repeatedly noninvasive hyperthermia mediated by pegylated silica-core gold nanoshells (pSGNs) in vivo with external near-infrared (NIR) laser irradiation. This study demonstrated that repeated photothermal treatment can effectively eliminate intraperitoneal tumors in mouse ovarian cancer models without damage of normal tissues. By conjugating pSGNs with anti-human CD47 monoclonal antibody, a significant photoablative effect can be achieved using lower amount of pSGNs and shorter NIR laser irradiation. Conjugated pSGNs specifically targeted and bound to cancer cells inside the peritoneal cavity. Our results indicate the possibility of a noninvasive method of repeated hyperthermia and photoablative therapies using nanoparticles. This has substantial clinical potential in treating ovarian and other intraperitoneal cancers.