Naturally biocompatible melanin based iron-complex nanoparticles for pH-responsive magnetic resonance imaging

Area of Science:

• Biomedical Imaging
• Nanotechnology
• Materials Science

Background:

• Magnetic resonance imaging (MRI) sensitivity relies on contrast agent (CA) relaxation and accumulation.
• Iron (Fe)-complexes are explored as alternatives to gadolinium (Gd)-based CAs due to better biocompatibility.
• Nanoparticle CAs show superior longitudinal relaxation but face challenges in tumor-specific accumulation.

Purpose of the Study:

• To develop a novel pH-responsive nanoparticle contrast agent for enhanced tumor MRI.
• To improve CA accumulation in tumors by utilizing the acidic tumor microenvironment.
• To evaluate the diagnostic potential of the new Fe-based CA.

Main Methods:

• Modification of melanin with poly(2-ethyl-2-oxazoline) (PEOz) for Fe(III) chelation, creating Fe(III)-Mel-PEOz.
• Exploiting pH-triggered surface charge switching (anion to cation) for enhanced tumor cell endocytosis.
• Assessing relaxation properties (r1) and cytotoxicity of Fe(III)-Mel-PEOz.
• Evaluating *in vivo* contrast enhancement and biocompatibility.

Main Results:

• Fe(III)-Mel-PEOz demonstrated pH-responsive charge switching, increasing tumor cell uptake.
• The agent maintained a stable longitudinal relaxivity (r1) of ~1.0 mM⁻¹s⁻¹ at 0.5 T, irrespective of pH changes.
• Fe(III)-Mel-PEOz exhibited low cytotoxicity and significant *in vivo* positive contrast enhancement in tumors.
• The nanoparticle showed excellent biocompatibility and stable relaxation properties.

Conclusions:

• Fe(III)-Mel-PEOz is a promising pH-responsive nanoparticle contrast agent for MRI.
• Its tumor-specific accumulation and enhanced relaxivity improve diagnostic accuracy.
• The agent's biocompatibility and low toxicity support its potential for clinical translation in tumor diagnosis.