Iron-Loaded Magnetic Nanocapsules for pH-Triggered Drug Release and MRI Imaging

Abstract

Magnetic nanocapsules were synthesized for controlled drug release, magnetically assisted delivery, and MRI imaging. These magnetic nanocapsules, consisting of a stable iron nanocore and a mesoporous silica shell, were synthesized by controlled encapsulation of ellipsoidal hematite in silica, partial etching of the hematite core in acid, and reduction of the core by hydrogen. The iron core provided a high saturation magnetization and was stable against oxidation for at least 6 months in air and 1 month in aqueous solution. The hollow space between the iron core and mesoporous silica shell was used to load anticancer drug and a T₁-weighted MRI contrast agent (Gd-DTPA). These multifunctional monodispersed magnetic "nanoeyes" were coated by multiple polyelectrolyte layers of biocompatible poly-l-lysine and sodium alginate to control the drug release as a function of pH. We studied pH-controlled release, magnetic hysteresis curves, and T₁/T₂ MRI contrast of the magnetic nanoeyes. They also served as MRI contrast agents with relaxivities of 8.6 mM^-1 s^-1 (r₁) and 285 mM^-1 s^-1 (r₂).

Figure 1

(A) Schematic showing the synthesis route of sodium alginate and poly-l-lysine coated nanoeye for pH triggered drug release, (B) SEM image of α-Fe₂O₃ nanorice, (C) TEM image of silica coated iron nanoeyes (Fe@SiO₂), (D) TEM image of sodium alginate and poly-l-lysine coated Fe@SiO₂ nanoparticles (Fe@SiO₂@AL/PLL) in low magnification, (E) TEM image of sodium alginate and poly-l-lysine coated Fe@SiO₂ nanoparticles (Fe@SiO₂@AL/PLL) in high magnification.

Figure 2

XRD pattern of (A) α-Fe@SiO₂, (B) α-Fe@SiO₂ in the air for 6 months, (C) (Fe/DOX/Gd-DTPA)@SiO₂@AL/PLL, (D) (Fe/DOX/Gd-DTPA)@SiO₂@AL/PLL in PBS buffer for a month.

Figure 3

ζ-Potentials of the PLL/AL multilayer coated Fe@SiO₂ nanocapsules as a function of the layer number.

Figure 4

FTIR spectra of (A) poly-l-lysine, (B) sodium alginate, (C) Fe@SiO₂, and (D) poly-l-lysine and sodium alginate coated Fe@SiO₂.

Figure 5

pH-triggered DOX release profile of DOX from (Fe/DOX/Gd-DTPA)@SiO₂@AL/PLL nanocapsules.

Figure 6

(A) Cytotoxicity test of iron core after removing silica coating (Fe), silica shell (SiO₂), silica coated iron nanocore (Fe@SiO₂), and alternating layers of PLL and AL coated magnetic nanocapsules (Fe@SiO₂@PLL/AL). (B) Cell viability of MCF-7 cells after incubating with different drug formulations at different concentrations for 48 h.

Figure 7

Magnetic hysteresis loop of Fe@SiO₂ and (Fe/DOX/Gd-DTPA)@SiO₂@AL/PLL.

Figure 8

T₁ (A) and T₂ (B)-weighted images of magnetic at echo time of 4 ms.