Micellar Iron Oxide Nanoparticles Coated with Anti-Tumor Glycosides.

Hugo Groult,Lorenzo Romero-Ramírez,Manuel Nieto-Sampedro,Isabel García-Álvarez,Fernando Herranz,Alfonso Fernández-Mayoralas,Jesús Ruiz-Cabello

doi:10.3390/nano8080567

Abstract

The synthesis procedure of nanoparticles based on thermal degradation produces organic solvent dispersible iron oxide nanoparticles (OA-IONP) with oleic acid coating and unique physicochemical properties of the core. Some glycosides with hydrophilic sugar moieties bound to oleyl hydrophobic chains have antimitotic activity on cancer cells but reduced in vivo applications because of the intrinsic low solubility in physiological media, and are prone to enzymatic hydrolysis. In this manuscript, we have synthetized and characterized OA-IONP-based micelles encapsulated within amphiphilic bioactive glycosides. The glycoside-coated IONP micelles were tested as Magnetic Resonance Imaging (MRI) contrast agents as well as antimitotics on rat glioma (C6) and human lung carcinoma (A549) cell lines. Micelle antimitotic activity was compared with the activity of the corresponding free glycosides. In general, all OA-IONP-based micellar formulations of these glycosides maintained their anti-tumor effects, and, in one case, showed an unusual therapeutic improvement. Finally, the micelles presented optimal relaxometric properties for their use as T2-weighed MRI contrast agents. Our results suggest that these bioactive hydrophilic nano-formulations are theranostic agents with synergistic properties obtained from two entities, which separately are not ready for in vivo applications, and strengthen the possibility of using biomolecules as both a coating for OA-IONP micellar stabilization and as drugs for therapy.

Highlights

Nanotechnology has important applications in biomedicine, mainly in the field of cancer treatment [1]
Oleic Acid-Coated IONP (OA-IONP) were synthetized at high temperature by thermal degradation of iron organic precursors blended with the OA surfactant
These values are comparable to previously reported IONP prepared with similar synthesis and confirmed the high control on size and uniformity of the particles provided by thermal degradation method [34,35]

Summary

Introduction

Nanotechnology has important applications in biomedicine, mainly in the field of cancer treatment [1]. The use of nanotechnology introduces targeting options either by passive accumulation of the NP inside tumor cells resulting from enhanced permeability and retention effect (EPR) or active ligand-mediated targeting [4,5,6]. Suitable targeting agents often improve pharmacokinetics, e.g., local delivery with improved dosing, membrane permeation as well as a reduced toxicity or minimum side effects by specific release of the therapeutic cargo in the target tissues [7,8]. Within the large number of nanomaterials, superparamagnetic iron oxides (IONP) are interesting for their capability to direct drugs at the pathological area mediated by an external, internally implanted, or even spatially directed magnetic field [9,10]. There is a growing interest in the use of IONP for hyperthermia applications [15]

Methods

Results

Discussion

Conclusion