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. 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, PPEGylated 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.