Enhanced thermodynamic, pharmacokinetic and theranostic properties of polymeric micelles via hydrophobic core-clustering of superparamagnetic iron oxide nanoparticles

Abstract

Background Superparamagnetic iron oxide nanoparticles (SPIO) have been applied for decades to design theranostic polymeric micelles for targeted cancer therapy and diagnostic MR imaging. However, the effects of SPIO on the physicochemical, and biological properties of polymeric micelles have not yet been fully elucidated. Therefore, we investigated potential effect of SPIO on the physical and biological properties of theranostic polymeric micelles using representative cancer drug (doxorubicin; Doxo) and polymer carrier (i.e., poly (ethylene glycol)-co-poly(D,L-lactide), PEG-PLA). Methods SPIO were synthesized from Fe(acetyl acetonate)3 in an aryl ether. SPIO and Doxo were loaded into the polymeric micelles by a solvent-evaporation method. We observed the effect of SPIO-clustering on drug loading, micelle size, thermodynamic stability, and theranostic property of PEG-PLA polymeric micelles. In addition, cellular uptake behaviors, pharmacokinetic and biodistribution study were performed. Results SPIO formed hydrophobic geometric cavity in the micelle core and significantly affected the integrity of micelles in terms of micelle size, Doxo loading, critical micelle concentration (CMC) and in vitro dissociation. In vivo pharmacokinetic studies also showed the enhanced Area Under Curve (AUC) and elongated the half-life of Doxo. Conclusions Clustered SPIO in micelles largely affects not only MR imaging properties but also biological and physical properties of polymeric micelles.

Magnetic Micellar Nanovehicles: Prospects of Multifunctional Hybrid Systems for Precision Theranostics

“…Micelle size is influenced both by the size [ 21 , 49 , 83 , 84 ] and the clustering [ 86 ] of loaded SPIONs. For a given SPION-loaded amount, increasing SPIONs size leads to an enlargement of MPMs.…”

“…For a given SPION-loaded amount, increasing SPIONs size leads to an enlargement of MPMs. The amount of loaded SPIONs also influences the micelle diameter, as elegantly investigated by Jiang et al [ 86 ]. In this work, the SPION-free micelles presented a diameter of 24 ± 3 nm, and the diameters increased to 80 ± 13, 100 ± 9 and 108 ± 8 nm, respectively, when SPIONs were loaded into the micelles by weight ratio of 15, 30, and 50% [ 86 ].…”

“…SPIONs significantly decrease the signal intensity by shortening the hydrogen transverse relaxation time ( T 2 ) causing the darkening of the interfered regions. The incorporation of SPIONs within micelles successfully enhances the MRI signal by increasing the magnetization per carrier, allowing a much more significant response to magnetic fields and thus an enhancement in MRI sensitivity [ 38 , 79 , 86 , 107 ].…”

“…Together with the payload delivery, the loading profile can be controlled and improved by magnetic field action. The incorporation of SPIONs in micellar systems of PLA-PEG significantly increased the content and loading efficiency of DOX [ 86 ]. The loading of DOX increased from 3.3 ± 2.0% to 12.4% when 15% wt SPIONs were co-loaded in the micelles.…”

Superparamagnetic Nanocrystals Clustered Using Poly(ethylene glycol)-Crosslinked Amphiphilic Copolymers for the Diagnosis of Liver Cancer

“…To enhance the quality of MRI, researchers have proposed the use of amphiphilic polymers to encapsulate hydrophobic SPIO nanocrystals and facilitate their dispersion in aqueous solutions through micelle formation [ 2 , 11 , 12 ]. Moreover, several studies have shown that these strategies have significant potential for improving the sensitivity of MRI [ 13 , 14 , 15 ]. A significant enhancement in T 2 relaxivity (r 2 ) can be achieved using synergistic magnetism through the encapsulation of multiple SPIO nanocrystals in the hydrophobic core of micelles to form magnetic nanoclusters [ 16 , 17 ].…”