A Multifunctional Nanoplatform for Imaging, Radiotherapy, and the Prediction of Therapeutic Response

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 11; no. 7; pp. 834 - 843
• Main Authors: McQuade, Casey, Al Zaki, Ajlan, Desai, Yaanik, Vido, Michael, Sakhuja, Timothy, Cheng, Zhiliang, Hickey, Robert J., Joh, Daniel, Park, So-Jung, Kao, Gary, Dorsey, Jay F., Tsourkas, Andrew
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 18.02.2015; Wiley Subscription Services, Inc
• Subjects: Animals; Cell Line, Tumor; Dextrans - pharmacokinetics; Dextrans - pharmacology; Diagnostic Imaging; DNA Breaks, Double-Stranded - drug effects; Female; Gold; Gold - pharmacokinetics; Gold - pharmacology; Humans; Imaging; iron oxide; Iron oxides; Kaplan-Meier Estimate; Magnetic resonance; Magnetite Nanoparticles; Medical imaging; Mice; Mice, Nude; Micelles; Nanoparticles; Nanoparticles - chemistry; Nanostructure; Nanotechnology; Polymers - chemistry; Radiation therapy; Radiation-Sensitizing Agents - pharmacology; Radiotherapy; Receiving; Tissue Distribution - drug effects; Treatment Outcome; Tumors; gold; iron oxide; magnetic resonance; nanoparticles; radiation therapy
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.201401927

Gold nanoparticles have garnered interest as both radiosensitzers and computed tomography (CT) contrast agents. However, the extremely high concentrations of gold required to generate CT contrast is far beyond that needed for meaningful radiosensitization, which limits their use as combined therapeutic–diagnostic (theranostic) agents. To establish a theranostic nanoplatform with well‐aligned radiotherapeutic and diagnostic properties for better integration into standard radiation therapy practice, a gold‐ and superparamagnetic iron oxide nanoparticle (SPION)‐loaded micelle (GSM) is developed. Intravenous injection of GSMs into tumor‐bearing mice led to selective tumoral accumulation, enabling magnetic resonance (MR) imaging of tumor margins. Subsequent irradiation leads to a 90‐day survival of 71% in GSM‐treated mice, compared with 25% for irradiation‐only mice. Furthermore, measurements of the GSM‐enhanced MR contrast are highly predictive of tumor response. Therefore, GSMs may not only guide and enhance the efficacy of radiation therapy, but may allow patients to be managed more effectively. Gold‐ and superparamagnetic iron oxide nanoparticle‐loaded polymeric micelles (GSM) enable magnetic resonance (MR) imaging and radiosensitization of tumors. GSM‐enhanced MR imaging is highly predictive of tumor response and subjects receiving GSMs in combination with radiation treatment have a longer mean survival than subjects receiving radiation alone.