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

Abstract

The treatment of glioblastoma multiforme, the most prevalent and lethal form of brain cancer in humans, has been limited in part by poor delivery of drugs through the blood-brain barrier and by unclear delineation of the extent of infiltrating tumor margins. Nanoparticles, which selectively accumulate in tumor tissue due to their leaky vasculature and the enhanced permeability and retention effect, have shown promise as both therapeutic and diagnostic agents for brain tumors. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) have been leveraged as T2-weighted MRI contrast agents for tumor detection and imaging; and gold nanoparticles (AuNP) have been demonstrated as radiosensitizers capable of propagating electron and free radical-induced radiation damage to tumor cells. In this study, we investigated the potential applications of novel gold and SPION-loaded micelles (GSMs) coated by polyethylene glycol-polycaprolactone (PEG-PCL) polymer. By quantifying gh2ax DNA damage foci in glioblastoma cell lines, we tested the radiosensitizing efficacy of these GSMs, and found that GSM administration in conjunction with radiation therapy (RT) led to ~2-fold increase in density of double-stranded DNA breaks. For imaging, we used GSMs as a contrast agent for both computed tomography (CT) and magnetic resonance imaging (MRI) studies of stereotactically implanted GBM tumors in a mouse model, and found that MRI but not CT was sufficiently sensitive to detect and delineate tumor borders after administration and accumulation of GSMs. These results suggest that with further development and testing, GSMs may potentially be integrated into both imaging and treatment of brain tumors, serving a theranostic purpose as both an MRI-based contrast agent and a radiosensitizer.

Progress in Polymeric Nano-Medicines for Theranostic Cancer Treatment

“…The prepared LPHs, having particle sizes of 20-30 nm and quantum yield of ≈50%, indicated bright fluorescence because of the insertion of lipid tail in polymeric core and resulted in an augment of space and intrachain quenching. Sun et al [91] used gold NPs and SPION-loaded micelles for in vitro detection of glioblastoma multiforme (brain cancer). These NPs were used as a contrast agent in computed tomography and MRI.…”

The Rational Design and Biological Mechanisms of Nanoradiosensitizers

“…PEG-decorated GNPs (12 nm) increased cellular DNA damage under irradiation in human GBM-derived cell lines and enhanced the survival of orthotopic GBM tumor-bearing mice [81]. Gold and superparamagnetic iron oxide nanoparticles (SPION)-loaded micelles (GSMs, 100 nm) in combination with radiotherapy led to an~2-fold increase in DSBs in GBM cells [82]. The combination of Au@Se NPs (120 nm) treatment with irradiation induced DNA damage by enhancing ROS generation and the phosphorylation levels of related proteins, including Ataxia-telangiectasia mutated (ATM), Checkpoint kinase 2 (Chk2), Breast cancer susceptibility protein 1 (BRCA1), p53 and histones [37].…”

Gold Nanoparticles as X-Ray, CT, and Multimodal Imaging Contrast Agents: Formulation, Targeting, and Methodology

“…The heteroparticle possessed a 3 : 1 gold : iron oxide ratio by mass while still possessing a high T 2 relaxivity (221.92 s −1 mM −1 ). This gave it excellent contrast in MR scans of both areas of interest, but the CT scans showed negligible differences [119]. Wang et al designed a large PEG micelle with encapsulated Fe 3 O 4 particles and a gold shell.…”