Nickel Nanoparticles in Biology and Medicine: Synthesis and Role

Nickel nanoparticles (NiNPs) have gained attention for applications in drug delivery, antimicrobial treatments, and cancer therapy. Their high surface area and catalytic activity make them valuable in biomedical research, but concerns about toxicity and biocompatibility necessitate a thorough understanding of their synthesis and biological interactions.

Advancements in production techniques aim to enhance efficiency, safety, and sustainability. Understanding their synthesis, characterization, and interactions with biological systems is crucial for optimizing medical applications while minimizing risks.

Conventional Production Routes

Nickel nanoparticles (NiNPs) have been synthesized through conventional methods for decades, allowing precise control over particle size, morphology, and stability. Chemical reduction remains a dominant approach, producing uniform, high-purity nanoparticles. This method typically involves reducing nickel salts like nickel chloride (NiCl₂) or nickel sulfate (NiSO₄) with reducing agents such as sodium borohydride (NaBH₄) or hydrazine (N₂H₄). Reaction conditions—temperature, pH, and surfactant presence—significantly influence nanoparticle characteristics. Adjusting these parameters can yield NiNPs ranging from a few nanometers to several hundred nanometers, impacting their reactivity and biomedical applications.

Thermal decomposition provides another route, particularly for high-crystallinity, well-dispersed nanoparticles. This method breaks down organometallic precursors like nickel acetylacetonate at elevated temperatures in the presence of stabilizing agents such as oleylamine or trioctylphosphine. Controlled heating produces monodisperse nanoparticles with well-defined shapes, making them useful for applications requiring consistent catalytic or magnetic properties. Research shows that thermal decomposition yields NiNPs with narrow size distributions, ensuring reproducibility in biomedical studies.

Electrodeposition leverages electrochemical principles to generate NiNPs on conductive substrates. By adjusting voltage, electrolyte composition, and deposition time, researchers fine-tune nanoparticle size and density. This method is particularly relevant for biosensor development, integrating NiNPs into electrochemical detection platforms. Studies highlight electrodeposition’s effectiveness in producing highly adherent NiNP coatings that enhance sensor sensitivity and stability while minimizing the need for organic solvents, reducing cytotoxicity concerns.

Green Synthesis Strategies

Eco-friendly synthesis methods have gained traction due to concerns over the environmental and biological hazards of conventional techniques. Green synthesis emphasizes non-toxic reagents, biodegradable stabilizers, and sustainable reaction conditions. Natural extracts from plants, bacteria, fungi, and algae serve as alternatives to traditional reducing and stabilizing agents, offering a biologically inspired approach. These biological entities contain phytochemicals, proteins, and enzymes that facilitate nickel ion reduction and nanoparticle stabilization.

Plant-mediated synthesis has attracted attention due to the bioactive compounds in botanical extracts, such as flavonoids, terpenoids, alkaloids, and phenolic acids. These molecules act as both reducing and capping agents, converting nickel salts into nanoparticles while preventing aggregation. Extracts from plants like Azadirachta indica (neem), Camellia sinensis (green tea), and Aloe vera generate NiNPs with well-defined morphologies and enhanced biocompatibility. Reaction conditions, including extract concentration, pH, and temperature, influence nanoparticle size and stability. Research in Materials Science and Engineering C shows plant-derived NiNPs exhibit antimicrobial properties, making them potential candidates for wound healing and infection control.

Microbial synthesis leverages bacteria and fungi to mediate nanoparticle formation. Species such as Bacillus subtilis, Pseudomonas aeruginosa, and Aspergillus niger possess enzymatic systems that facilitate metal ion reduction, leading to intracellular or extracellular NiNP production. This biosynthetic route offers scalability and precision, as microbial cultures can be optimized for controlled nanoparticle size distributions. A study in Applied Microbiology and Biotechnology found NiNPs synthesized by Pseudomonas stutzeri demonstrated strong catalytic activity, highlighting their biomedical and industrial potential.

Algae-based synthesis utilizes the high metal-binding affinity of algal biomolecules, including polysaccharides, proteins, and pigments. Marine and freshwater algae, such as Chlorella vulgaris and Spirulina platensis, facilitate nickel ion reduction through biosorption and enzymatic interactions, stabilizing NiNPs and enhancing dispersion. Research in Green Chemistry indicates algae-derived NiNPs exhibit antioxidant activity, potentially mitigating oxidative stress-related disorders. The use of algae aligns with circular bioeconomy principles, as these organisms can be cultivated using wastewater or carbon dioxide sequestration strategies, further enhancing sustainability.

Key Structural Features

Nickel nanoparticle (NiNP) structure influences their functionality in biological and medical applications, affecting surface reactivity, stability, and bioavailability. Size plays a crucial role, with smaller particles exhibiting higher surface area-to-volume ratios, enhanced catalytic activity, and increased biological interactions. Controlling nanoparticle size is essential for tailoring their therapeutic and diagnostic behavior, as variations impact cellular uptake and biodistribution.

Shape also affects physicochemical behavior. Spherical NiNPs are commonly synthesized due to their uniformity and ease of suspension in biological media, but alternative morphologies such as nanorods, nanocubes, and hollow nanospheres offer specialized applications. Anisotropic NiNPs, such as nanowires, exhibit superior magnetic properties, making them useful in targeted drug delivery and magnetic resonance imaging (MRI) contrast enhancement. Shape influences surface energy, affecting aggregation and cellular internalization.

Surface chemistry further refines functionality. Modifications with ligands, polymers, or biocompatible coatings improve stability and reduce side effects. Surface passivation with polyethylene glycol (PEG) or chitosan enhances dispersion in physiological environments and prolongs circulation time. Functionalization with biomolecules, such as antibodies or peptides, enables targeted delivery to specific tissues. Engineering surface properties allows precise control over NiNP interactions, optimizing their efficacy in drug delivery and biosensing.

Characterization Procedures

Assessing the structural and physicochemical properties of nickel nanoparticles (NiNPs) ensures consistency, functionality, and safety in biomedical applications. Advanced analytical techniques examine size distribution, morphology, crystallinity, surface chemistry, and magnetic behavior.

Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) visualize nanoparticle shape and surface topology. TEM provides detailed core structure and dispersion insights, while SEM offers three-dimensional surface imaging, useful for evaluating roughness and uniformity.

Dynamic light scattering (DLS) quantifies particle size and distribution, measuring the hydrodynamic diameter in suspension. Unlike electron microscopy, which captures static images, DLS provides real-time data on behavior in biological fluids, revealing aggregation tendencies. X-ray diffraction (XRD) confirms crystalline structure, identifying phase composition and purity. Specific diffraction peaks associated with nickel’s face-centered cubic (FCC) lattice verify nanoparticle integrity for biomedical use.

Surface chemistry plays a crucial role in biological interactions. Fourier-transform infrared spectroscopy (FTIR) identifies functional groups on the nanoparticle surface, distinguishing coatings or stabilizers that influence biocompatibility. X-ray photoelectron spectroscopy (XPS) further refines analysis by probing elemental composition and oxidation states, assessing reactivity and stability. These characterization techniques optimize NiNP formulations for therapeutic or diagnostic applications.

Biological Interactions

Nickel nanoparticles (NiNPs) interact with biological systems based on their physicochemical properties, influencing cellular uptake, biodistribution, and therapeutic or toxicological effects. Their small size and high surface energy facilitate membrane interactions, leading to various endocytic pathways. Once internalized, NiNPs can localize within organelles such as lysosomes and mitochondria, triggering biochemical responses. Surface coatings and functionalization strategies significantly alter these interactions, affecting cellular compatibility and pharmacokinetics.

Polyethylene glycol (PEG)-coated NiNPs exhibit prolonged circulation times and reduced aggregation, making them suitable for drug delivery. Conversely, uncoated NiNPs may induce oxidative stress by generating reactive oxygen species (ROS), leading to cytotoxic effects.

Dissolution properties also influence bioactivity, as nickel ions released from nanoparticles engage in distinct biochemical pathways. Soluble nickel has been associated with activating stress response proteins and inflammatory mediators, contributing to cytotoxic or immunomodulatory effects. Research in Toxicology and Applied Pharmacology shows NiNPs with higher dissolution rates elicit stronger cellular responses, making stability a critical factor in biomedical applications. Aggregation in biological fluids impacts biodistribution, affecting retention in tissues such as the liver, lungs, and kidneys. Understanding these interactions is essential for designing NiNPs that balance therapeutic efficacy with minimal adverse effects, ensuring safe integration into medical technologies.