Silica-Coated Metal Chelating-Melanin Nanoparticles as a Dual-Modal Contrast Enhancement Imaging and Therapeutic Agent

Abstract

Bioinspired melanin nanoparticle (Mel NP) synthesized with dopamine has been of great interest in various biomedical applications. However, the utilization of fascinating characters of Mel NP such as innate MR contrast effects, high affinity to metal ions, strong light absorption requires special design with strategic synthetic method for its own purpose. Here, we have introduced paramagnetic Gd3+ metal ions and silica nanocoating on Mel NP for the dual-modal MRI/fluorescent contrast-enhanced imaging and therapeutics. The Gd3+ chelating kinetics of Mel NP by quinone and hydroquinone residues were optimized in various conditions of Gd3+ amounts and pH in solution for improving MRI contrast enhancing properties of the Mel NP. Then, bioinert silica was coated on the surfaces of Gd-chelated Mel NP (Gd-Mel@SiO2 NP) with a modified sol–gel process. The silica nanocoating allowed increased outer sphere water diffusion time, resulting a significantly brighter MR T1 contrast effect of Gd-Mel@SiO2 NP, comparing with a bare Gd-Mel NP or clinical grade T1 contrast agent. Further, when the Gd-Mel@SiO2 NP was labeled with fluorescent molecules, a significantly enhanced fluorescent intensity was achieved by the silica nanocoating that preventing the innate fluorescent deactivation property of melanin. Finally, in vitro/in vivo dual-modal contrast enhanced MRI/fluorescent imaging and feasibility of image-guided cancer therapeutic applications using Gd-Mel@SiO2 NPs were successfully evaluated in a clinically relevant human prostate cancer xenograft mouse model.

Novel Intrapolymerization Doped Manganese‐Eumelanin Coordination Nanocomposites with Ultrahigh Relaxivity and Their Application in Tumor Theranostics

“…In a typical synthesis, approximately 50 mg products could be obtained, determined by weighing after lyophilization. The Mn loading efficiency reached 10.2% wt/wt (Table S1, Supporting Information), which is much higher than previous studies 13, 29, 32, 33. It suggests more efficient synthesis and higher yields than conventional PPD approaches.…”

Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus of Colloidal Polydopamine Prepared by Carbon Dot Stimulated Polymerization of Dopamine

“…Another important feature of PDA is its antimicrobial property, as PDA binds a cell membrane to form a barrier on a cell surface to prevent the diffusion of nutrients and wastes in or out of the cell cytosol, leading to cell lysis. PDA is an important polymer with excellent biocompatibility and low cytotoxicity, which can be used for various applications [28][29][30] including biological/medicinal applications [31,32]. The PDA composites, particularly those decorated with metal oxides, have been used for cancer therapy and antibacterial treatments.…”

Melanin‐Like Nanomaterials for Advanced Biomedical Applications: A Versatile Platform with Extraordinary Promise

“…MelNPs exhibit high binding affinity toward various metal ions, attributed to the presence of abundant sites for metal coordination, including amine, carboxy, o ‐quinone, semiquinone, phenolic groups, and nitrogen atoms on their surface 11. Inspired by this, MelNPs have been extensively employed as building blocks for chelating various paramagnetic metal ions (e.g., gadolinium,26 manganese,27 and iron28) as MR contrast agents, without requiring additional extrinsic chelators.…”

“…Usually, these MelNPs were first fabricated via enzymatic or chemical oxidation and polymerization of applicable precursors (e.g., tyrosine, dopamine) in alkaline environment (e.g., ammonium hydroxide, sodium hydroxide) and specific organic solvents 28a,36b,56. Then, metal ions (e.g., gadolinium,26 manganese,27 and iron28b) were anchored onto the as‐prepared MelNPs. This procedure is designated as post‐polymerization doping strategy.…”

“…Inspired by the intrinsic photoacoustic property and excellent metal ion chelation ability, Mn 2+ ‐chelated MelNPs have been widely explored for MRI/PAI guided PTT applications 36a,56,58a. Similarly, Gd 3+ ‐chelated and bioinert silica coated MelNPs (TRITC‐Gd‐Mel@SiO 2 NPs) were also reported for MRI/fluorescence imaging guided tumor PTT 26. The silica nanocoating could not only provide improved T 1 MR contrast comparing with bare Gd‐Mel NPs, but also prevent the innate fluorescent quenching effect of melanin when labeled with fluorescent molecules.…”