Double-Layer Fatty Acid Nanoparticles as a Multiplatform for Diagnostics and Therapy

Abstract

Today, public health is one of the most important challenges in society. Cancer is the leading cause of death, so early diagnosis and localized treatments that minimize side effects are a priority. Magnetic nanoparticles have shown great potential as magnetic resonance imaging contrast agents, detection tags for in vitro biosensing, and mediators of heating in magnetic hyperthermia. One of the critical characteristics of nanoparticles to adjust to the biomedical needs of each application is their polymeric coating. Fatty acid coatings are known to contribute to colloidal stability and good surface crystalline quality. While monolayer coatings make the particles hydrophobic, a fatty acid double-layer renders them hydrophilic, and therefore suitable for use in body fluids. In addition, they provide the particles with functional chemical groups that allow their bioconjugation. This work analyzes three types of self-assembled bilayer fatty acid coatings of superparamagnetic iron oxide nanoparticles: oleic, lauric, and myristic acids. We characterize the particles magnetically and structurally and study their potential for resonance imaging, magnetic hyperthermia, and labeling for biosensing in lateral flow immunoassays. We found that the myristic acid sample reported a large r2 relaxivity, superior to existing iron-based commercial agents. For magnetic hyperthermia, a significant specific absorption rate value was obtained for the oleic sample. Finally, the lauric acid sample showed promising results for nanolabeling.

Keywords: biosensor; inductive sensing; lateral flow immunoassays; magnetic hyperthermia; magnetic nanoparticles; magnetic relaxation; magnetic resonance imaging.

Figure 1

(a) Scheme of the particles’ biofunctionalization process with neutravidin by the EDC/NHS chemistry. For simplification, only one functional group has been represented on the surface of the MNPs and the neutravidin. (b) Schematic view of a lateral flow strip and its test line: a neutravidin-MNP complex captured by a molecule of biotin. (c) Impedance variation for two scans of the OA@NP sample.

Figure 2

TEM images for samples (a) OA@NP, (b) LA@NP, and (c) MA@NP.

Figure 3

Magnetization curves at (a) 250 K and (b) 5 K for the three samples OA @NP, LA @NP, and MA@NP. The reduced remanence ($M_S/M_R$) at 5 K (see Table 2) is far from the theoretical value of 0.5 for non-interacting uniaxial single-domain particles, confirming the presence of non-negligible interparticle interactions, especially for MA@NP.

Figure 4

(a) ZFC–FC curves of the three samples. (b) δM curves calculated from $m^{\mathrm{IRM}}$ and $m^{\mathrm{DCD}}$ curves measured at 5 K. The inset graph shows the Henkel Plots for the three samples OA@NP, LA@NP, and MA@NP.

Figure 5

Temperature kinetics of water suspension of OA@NP (conc. 12.0 mg/mL), LA@NP (13.6 mg/mL), and MA@NP (27.5 mg/mL) exposed to an alternating field (17 kA/m amplitude and 183 kHz frequency).

Figure 6

(a) Magnetic signal obtained in the sensor for the LFA with neutravidin-conjugated LA@NP particles. The error bars show the standard deviation. The dashed lines serve as a guide to the eye. Inset: Percentage increase per mg of the magnetic signal in the sensor for the three samples. (b) Image of the 1 mg/mL of neutravidin LFA run with, from left to right, OA@NP, LA@NP, and MA@NP.

Figure 7

Test line sensor evaluation for the LFAs using LA@NP (black) and MA@NP (red) with 2 mg/mL neutravidin. The horizontal ticks represent 1 mm displacement steps. Bottom: Photographs of both LFAs. The blue arrow points at the peak corresponding to the particle accumulation in the LA@NP.