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

Abstract

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.

Actual questions raised by nanoparticle radiosensitization

“…For gold-loaded polymeric micelles, the first time point is 6h showing a 1.4 fold increase in foci numbers. At 12h, it reaches 2.2, confirming a timedependency (McQuade et al, 2015). For AGuIX ® , initial enhancement in foci number seems to depend on the cell line: at 30 min, no difference between exposed and control cells was noted with B16F10 (Kotb et al, 2016) while a 1.5 fold increase was mentioned for SQ20B (Miladi et al, 2015).…”

Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme

“…33–35 Laboratory stock chemicals, as well as iron and gold salts, were purchased from Sigma-Aldrich (St. Louis, MO, USA). In brief, dodecanethiol-capped AuNPs ( d = 1.9 nm) were prepared by reduction of gold salts in a two-phase reaction as described by Brust et al; 34 while oleic acid-stabilized SPIONs ( d = 15 nm) were prepared by thermal decomposition and precipitation in acetone as described by Park et al 35 …”

“…In particular, polyethylene glycol-polycaprolactone (PEG-PCL) is an FDA-approved biodegradable amphiphilic diblock co-polymer that can deter membrane opsonization and improve circulation times. 25, 33 …”

Targeted nanoparticles for tumour radiotherapy enhancement—the long dawn of a golden era?

“…Electron-dense materials such as gold were proven to be suited for this purpose in a series of in vitro and in vivo studies [e.g., (10)(11)(12)(13)(14)(15)]. It is important to point out here that gold NP do not per se alter the cellular radiosensitivity of a tumour.…”