Exploring the Role of Polyethylene Glycol in Nanotechnology

Nanotechnology, as an emerging science, is rapidly changing our understanding of materials and structures. From drug delivery systems to electronic devices, the range of applications for nanotechnology is vast and holds enormous potential. In this field, polyethylene glycol (PEG) is an important material that has become an indispensable part of nanotechnology due to its unique chemical properties and multifunctionality. This article will explore various applications of polyethylene glycol in nanotechnology and look ahead to its future development directions.

What is Polyethylene Glycol?

Polyethylene glycol is a linear polymer composed of repeating ethylene oxide units. The molecular weight of PEG can vary, influencing its physical and chemical properties. Due to its multiple hydroxyl groups, PEG is highly hydrophilic and easily dissolves in water. The molecular weight of PEG can range from hundreds to millions, making it versatile across various applications. Traditionally, PEG has been widely used in the pharmaceutical, cosmetic, and food industries as a solubilizer, stabilizer, and lubricant. However, with the development of nanotechnology, the unique properties of PEG have made it a key component in the design and application of nanomaterials.

Polyethylene Glycol Derivatives

Polyethylene Glycol Nanoparticles

PEG nanoparticles are nanometer-sized particles made from PEG polymers, widely used in drug delivery, gene transfer, medical imaging, and diagnostics. The hydrophilicity and biocompatibility of PEG allow these nanoparticles to evade recognition and clearance by the immune system, improving the bioavailability and therapeutic efficacy of drugs. By modifying the surface of nanoparticles with PEG, a so-called "stealth" barrier is created, allowing the particles to remain in circulation for a longer time and avoiding phagocytic clearance. PEG nanoparticles not only carry drugs but also improve drug solubility, control release rates, and enhance targeted delivery to specific sites. Therefore, PEG nanoparticles have significant potential in applications such as targeted therapy, vaccine delivery, and cancer treatment. With the development of nanotechnology, PEG nanoparticles have become a key carrier in precision medicine and nanomedicine.

Fig. 1. Liposomal drug delivery with polyethylene glycol.

PEGylated Nanoparticles

PEGylated nanoparticles refer to nanoparticles whose surfaces are modified with PEG molecules to improve their physicochemical properties. The main advantage of PEGylation is to enhance the solubility and stability of nanoparticles while reducing their immunogenicity in the body. The PEG molecules form a hydrated layer on the surface of nanoparticles, which effectively prevents aggregation and extends their circulation time in the body. In the preparation of PEGylated nanoparticles, chemical coupling methods are typically used to covalently attach PEG to the surface of the nanoparticles. For example, in liposome nanoparticles, PEG can react with lipid molecules to form PEGylated liposomes. These liposomes show significant advantages in drug delivery, improving the stability and targeting of the drug.

PEG Gold Nanoparticles

Gold nanoparticles are of great interest in biomedical fields due to their unique optical properties and good biocompatibility. PEGylated gold nanoparticles, by modifying the surface with PEG molecules, further enhance their stability and functionality in biological systems. PEGylated gold nanoparticles demonstrate excellent performance in bioimaging, serving as fluorescent probes or carriers for photothermal therapy. Furthermore, PEGylated gold nanoparticles can be used for targeted therapy. By modifying specific targeting ligands, such as antibodies or peptides, on the PEG chains, these nanoparticles can specifically bind to the surface of diseased cells for precise drug delivery. For example, in cancer treatment, PEGylated gold nanoparticles can carry anticancer drugs and directly target tumor cells, reducing damage to normal tissues.

PEG Hydrogel

PEG hydrogel is a three-dimensional network structure formed by the crosslinking of PEG molecules, offering excellent biocompatibility and tunable mechanical properties. Its unique hydrophilic nature gives it tremendous potential in tissue engineering and drug delivery. The properties of PEG hydrogels can be controlled by adjusting the crosslinking density, which in turn allows for the regulation of pore size and mechanical performance to meet specific application requirements. In nanotechnology, PEG hydrogels are often used as scaffold materials in tissue engineering. By embedding nanomaterials such as bioactive factors or drug carriers into the hydrogel, its functionality can be further enhanced. For example, embedding nanoparticles into PEG hydrogels can facilitate the sustained release of drugs, extending their duration of action. Furthermore, PEG hydrogels can be utilized in the development of biosensors by modifying their surface with specific recognition molecules to enable the detection of biomolecules.

PEG Coating Nanoparticles

The primary function of PEG coating is to enhance the biocompatibility and stability of nanoparticles. By forming a PEG layer on the surface of nanoparticles, this coating effectively prevents the immune system of the body from recognizing and eliminating the nanoparticles. This layer also reduces nanoparticle aggregation in the body and extends their circulation time, thereby improving their efficiency in drug delivery. PEG-coated nanoparticles have widespread applications in the pharmaceutical field. For instance, in targeted drug delivery, the PEG coating can protect the drug from degradation while enabling precise delivery through surface-modified targeting ligands. Additionally, PEG-coated nanoparticles can be used in diagnostic imaging, where the coating can incorporate contrast agents for high-resolution imaging of affected areas. In materials science, PEG-coated nanoparticles are also used in the development of novel composite materials. By modifying the surface of nanoparticles with PEG, the compatibility of the nanoparticles with matrix materials is improved, enhancing the mechanical properties and stability of the composite material.

Polyethylene Glycol Nanoemulsion

PEG nanoemulsion is an emulsion system stabilized by PEG molecules, which exhibits good stability and dispersibility. Its particle size is typically at the nanoscale, enabling efficient drug delivery and enhanced bioavailability. The stability of PEG nanoemulsions primarily stems from the protective layer formed by PEG molecules at the oil-water interface, which prevents particle aggregation and degradation. PEG nanoemulsions have broad applications in the cosmetics and food industries. For example, in cosmetics, PEG nanoemulsions can be used to deliver active ingredients such as vitamins and antioxidants, improving their stability and skin absorption rate. In the food industry, PEG nanoemulsions can be used to deliver fat-soluble nutrients like vitamin E and fish oil, enhancing their bioavailability. In the pharmaceutical field, PEG nanoemulsions are also used to develop novel drug delivery systems. By encapsulating drugs in PEG nanoemulsions, sustained release and targeted delivery of the drugs can be achieved. For instance, some anticancer drugs can be delivered via PEG nanoemulsions, reducing their distribution in normal tissues and increasing their concentration in tumor tissues.

How is Polyethylene Glycol Used in Nanotechnology?

PEG has several key applications in nanotechnology, including the surface modification of nanoparticles, construction of drug delivery systems, development of biosensors, and preparation of tissue engineering materials.

Surface Modification of Nanoparticles

PEGylation refers to the covalent attachment of PEG chains to the surface of nanoparticles to improve their physicochemical properties and biocompatibility. The flexibility and hydrophilicity of PEG chains help reduce the immune response to nanoparticles in the body and extend their circulation time. For example, DMPE-PEG-Biotin is a commonly used PEGylating reagent, where the hydrophobic tail interacts with the hydrophobic core of nanoparticles, and the PEG chain provides stability and biocompatibility. Additionally, thiol-PEG-stearic acid (SA-PEG-SH) is frequently used for surface modification, where its thiol group reacts with surface functional groups on nanoparticles to stabilize them.

Drug Delivery

In drug delivery systems, PEG enhances drug solubility, stability, and targeting efficiency. PEGylated lipid nanoparticles (LNPs) are key technologies in mRNA vaccine development. For instance, DMG-PEG-2000 is used to prepare lipid nanoparticles that significantly improve mucus permeability and delivery efficiency. Furthermore, PEGylated nanoparticles can enable targeted drug delivery through surface-modified targeting molecules. For example, a low-immunogenicity PEG nanoparticle developed by Professor Cui's team enables targeted delivery of therapeutic drugs for photothermal-immunotherapy. However, PEGylation presents challenges, such as accelerated blood clearance (ABC) phenomenon caused by repeated injections of PEGylated nanoparticles, which can reduce drug efficacy. To address this, researchers have developed strategies like using metal-organic framework materials (ZIF-8) as templates to prepare "stealth" PEG nanoparticles, mitigating the ABC effect.

Biosensors

PEG's application in biosensors mainly focuses on enhancing sensor stability and sensitivity. PEG chains reduce non-specific adsorption on the surface of biosensors, thereby improving selectivity and accuracy. For example, DSPE-PEG 2000-triglycine is a PEGylating reagent used for nanoparticle surface modification, with its triglycine sequence providing specific biological recognition functionality. Additionally, PEGylated gold nanoparticles are used in biosensor development, where PEG modification improves the dispersion and biocompatibility of the nanoparticles.

Tissue Engineering Materials

In tissue engineering, PEG is primarily used to construct biocompatible scaffold materials. For example, cellulose nanocrystal (CNC)-doped PEG-PVA nanocomposite films are prepared using electrospinning technology and exhibit excellent biocompatibility and mechanical properties. Furthermore, PEGylated nanofiber scaffolds are used in fields like skin tissue regeneration, with their good water absorption and degradation properties making them ideal materials for tissue engineering.

Immunological Effects and Safety

Despite the many advantages of PEGylation in nanotechnology, its immunological effects have raised concerns. Research by the Sui group indicates that PEGylated lipid nanoparticles may induce the body to produce anti-PEG antibodies, potentially affecting the in vivo distribution and pharmacokinetics of drugs. Therefore, when designing PEGylated nanomaterials, it is essential to consider their immunogenicity and biological safety.

Recent Advances and Future Directions

Recent advancements in PEG in nanotechnology focus on enhancing the stability, functionality, and biocompatibility of PEG-coated nanoparticles. Researchers have developed PEG-based hybrid materials that combine the advantages of PEG with other polymers or inorganic materials. These hybrid materials show enhanced mechanical properties and improved drug release characteristics, making them suitable for a wide range of biomedical applications. Another active research area is the development of stimulus-responsive PEG-based systems. These materials can alter their properties in response to environmental stimuli (such as pH, temperature, or enzymes), enabling controlled drug release and targeted therapy. For example, PEG-based hydrogels that degrade in response to specific enzymes have been developed for tissue engineering applications. In the future, the role of PEG in nanotechnology is expected to expand further. Advances in materials science and nanotechnology may lead to the development of PEG-based systems with enhanced performance and functionality. Additionally, the integration of PEG with emerging technologies, such as gene editing and artificial intelligence, could open new avenues for biomedical research and therapeutic applications.

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