Abstract 5380: Near-infrared-resonant IONP/Au2S core/satellites hybrid nanocomposite for imaging-guided photothermal therapy

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Abstract: Photothermal therapy (PTT) using near-infrared-resonant nanomaterials including multifunctional probes with both therapeutic functions and imaging capabilities has gained great attention in recent years. However, various challenges still exist including the large size of gold nanoshells, the “melting” effect of gold nanorods, lack of imaging capability, and tedious multiple steps for making imaging-capable multifunctional probes. Consequently, it is desired to develop an effective PTT mediator with the following criteria: small size, photo stability, facile synthesis, low toxicity, and imaging capability. We report the design of a core/satellites hybrid nanocomposite with a highly crystallized iron oxide nanoparticle (IONP) core (10-20 nm) and multiple gold sulfide (Au2S) nanoparticle satellites (1-2 nm) attached to the IONP polysiloxane-containing polymer coating for imaging-guided photothermal cancer therapy. In this nanostructure, the multiple satellites (Au2S) enhance PTT, while the IONP core serves as both a photothermal mediator and magnetic resonance imaging (MRI) contrast agent to localize the tumor. To make these core/satellites nanocomposites we first modify the IONP polymer coating with (3-mercaptopropyl) trimethoxysilane followed by mixing with Au2S nanoparticles, which are made by mixing sodium sulfide (Na2S) and chloroauric acid (HAuCl4) at the designed ratio. After purification using a magnet, the TEM image shows that around 8-10 Au2S nanoparticles (1-2 nm average diameter) were attached to each IONP (15 nm in diameter). This core/satellites nanocomposite has obvious absorption in the near infrared (NIR) range and the absorption peak can be adjusted by the molar ratio of Na2S to HAuCl4. The developed nanocomposite exhibits an enhanced photothermal effects without any quenching under NIR laser light. Benefitting from the anti-biofouling polysiloxane-containing polymer coating for in vivo applications, the core/satellites nanocomposites effectively accumulate to xenograft tumor tissue (SUM-159, triple-negative breast tumor cell line) through the enhanced permeability and retention effect after tail vein injection. MRI imaging is used to locate the tumors. NIR triggered PTT, which is enhanced by the core/satellites nanoparticles within the tumor site, destroys the tumor cells, while the tumor tissues in control mice do not show any change under the same laser light irradiation. Our in vitro and in vivo data reveal that NIR-resonant IONP/Au2S core/satellites nanocomposites can be used as effective MRI imaging-guided photothermal cancer therapy. Correspondence should be addressed to: Duxin Sun, PhD, or Hongwei Chen, PhD, Department of Pharmaceutical Sciences, College of Pharmacy, The University of Michigan, 428 Church Street, Ann Arbor, MI 48109, Email: duxins@umich.edu (D. Sun); or hongweic@umich.edu (H. Chen) Citation Format: Hongwei Chen, Joseph Burnett, Xiaoqing Ren, Feng Ni, Yi Wei, Hayley Paholak, Duxin Sun. Near-infrared-resonant IONP/Au2S core/satellites hybrid nanocomposite for imaging-guided photothermal therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5380. doi:10.1158/1538-7445.AM2014-5380