Structure and Function of Iron-Loaded Synthetic Melanin

Abstract

We describe a synthetic method for increasing and controlling the iron loading of synthetic melanin nanoparticles and use the resulting materials to perform a systematic quantitative investigation on their structure-property relationship. A comprehensive analysis by magnetometry, electron paramagnetic resonance, and nuclear magnetic relaxation dispersion reveals the complexities of their magnetic behavior and how these intraparticle magnetic interactions manifest in useful material properties such as their performance as MRI contrast agents. This analysis allows predictions of the optimal iron loading through a quantitative modeling of antiferromagnetic coupling that arises from proximal iron ions. This study provides a detailed understanding of this complex class of synthetic biomaterials and gives insight into interactions and structures prevalent in naturally occurring melanins.

Keywords: MRI; antiferromagnetic coupling; magnetometry; polymerization; synthetic melanin.

Figure 1

Representative electron microscopy characterization of SMNP-4: (a) TEM; (b) cryo-TEM; (c) SEM; and (d) HAADF-STEM (inset is the selected area EDS Fe elemental mapping image).

Figure 2

(a) ¹H NMRD profiles for SMNP-i (i = 1–5). The x-axis is the proton Larmor frequency; the y-axis is the r_1p value per Fe(III) ion (r_1p(Fe(III))) for each SMNP. (b) ¹H NMRD profiles for SMNP-i (i = 1–5). The x-axis is the proton Larmor frequency; the y-axis is the r_1p value per SMNP (r_1p(particle)).

Figure 3

T₁-weighted MR images captured on a Bruker 7.0 T magnet from SMNP-0, SMNP-1, and SMNP-4 in different media (particle concentration is 1.3 mg/mL in each tube). T₁ results for each phantom are shown below in milliseconds, respectively.

Figure 4

(a) Experimental EPR spectra of SMNP-i (i = 0–5). (b) Temperature-dependent EPR analysis of SMNP-5.

Figure 5

Temperature dependence of the product of magnetic susceptibility and temperature (χ_MT) for SMNP-i (i = 1–5). The dotted line describes the behavior of an isolated, isotropic Fe(III) ion. Solid lines represent a global fit of the data between 25 and 300 K as described in the text.

Figure 6

(a) Plot of variable-temperature variable-field magnetization data for SMNP-1. The color bar represents the difference between experimental data and fitting results. A standard 2D M vs H/T plot is shown in Figure S9b. (b) UV–vis spectra of 0.1 mg/mL SMNP showing the transition from a featureless absorption for SMNP-0 to a well-defined yet broad structure in SMNP-5. Absorption peaks for mono- (~710 nm), bis- (~570 nm), and tris-catechol (~490 nm) are identified by dashed green, blue, and red lines, respectively.

Scheme 1

Preparation of SMNP-i (i = 0–5) samples: (a) postdoping strategy for SMNP-1, (b) prepolymerization doping strategy for SMNP-2, SMNP-3, SMNP-4, and SMNP-5, and (c) SMNP-i (i = 0–5) samples with different Fe(III) concentrations.