The emergence of advanced nano-drug delivery systems has greatly optimized the field of drug research and development and provided new ideas for the treatment of various diseases. Among these nanodrug delivery system components, methoxypolyethylene glycolamine (mPEG-NH2) has attracted much attention due to its unique properties and versatility. mPEG-NH2 is a derivative of polyethylene glycol (PEG) with an amine functionality on one end and a methoxy group on the other. The structure possesses several favorable properties that make it well suited for drug delivery applications, including improved solubility, biocompatibility, and reduced immunogenicity. Studies have shown that loading drugs into mPEG-NH2 carriers can effectively improve the stability, bioavailability, and targeted delivery of drugs. These characteristics can help improve the therapeutic effect of drugs. Among these characteristics, mPEG-NH2 improves the solubility of hydrophobic drugs, which is a major advantage in drug delivery. Research shows that many of the drugs currently discovered are insoluble, which greatly limits their application scope and therapeutic effect. By combining these drugs with a nanocarrier system composed of mPEG-NH2, not only can their solubility be significantly enhanced, but also they can be more easily absorbed and distributed in the body. In addition, the PEG component of the system can form a protective hydrophilic shell around the drug molecule. It can protect the loaded drugs from being degraded by enzymes in the body and prevent the drugs from being cleared prematurely by the immune system. This protection not only prolongs the drug's half-life but also ensures a sustained release, leading to more consistent therapeutic effects over time.
Figure 1. mPEG-NH2 was immobilized on the surface of PES membrane to improve the biocompatibility of the material. (He T, et al.; 2021)
Furthermore, mPEG-NH2 offers a versatile platform for the design of targeted drug delivery systems. The amine group on mPEG-NH2 can be easily conjugated with various ligands, peptides, or antibodies that specifically bind to target cells or tissues. This targeted approach minimizes the off-target effects and enhances the accumulation of the drug at the desired site of action. For instance, in cancer therapy, mPEG-NH2 can be linked with tumor-specific antibodies, ensuring that the chemotherapeutic agent is delivered directly to the cancer cells, thereby maximizing its efficacy while minimizing damage to healthy tissues. Additionally, the stealth properties conferred by the PEG moiety help the drug-loaded nanoparticles evade recognition and clearance by the reticuloendothelial system, further improving their circulation time and therapeutic performance. The benefits of mPEG-NH2 extend beyond solubility enhancement and targeted delivery. Its biocompatibility and reduced immunogenicity are critical factors in its widespread adoption in drug delivery systems. PEGylation, the process of attaching PEG chains to molecules, is known to reduce the immunogenicity of therapeutic proteins and peptides, thereby decreasing the risk of immune responses that can lead to adverse effects or rapid clearance from the body. mPEG-NH2, with its specific functional groups, enables the precise and stable attachment of PEG to drugs, preserving their therapeutic activity while mitigating potential immunogenic reactions. This attribute is particularly valuable in the development of biopharmaceuticals, where maintaining the delicate balance between efficacy and safety is paramount.
In addition to enhancing the pharmacokinetic properties of drugs, mPEG-NH2 can facilitate the development of innovative drug delivery platforms such as liposomes, micelles, and nanoparticles. These delivery platforms can encapsulate drugs to protect them from degradation and achieve controlled release. Similarly, mPEG-NH2 functionalized micelles and nanoparticles have the potential for targeted delivery, as their surfaces can be modified with ligands, thereby directing them to specific cells or tissues. This versatility makes mPEG-NH2 an important tool for designing next-generation drug delivery systems. The flexibility of mPEG-NH2 in conjugation chemistry allows tailoring of drug delivery vehicles to meet specific therapeutic needs. The amine groups at the mPEG-NH2 termini can participate in a variety of chemical reactions, allowing the loaded drug to be attached via a stable linkage and released in response to specific triggers, such as changes in pH or the presence of certain enzymes. This targeted release mechanism can improve the precision of drug delivery, thereby ensuring that the drug is released at the site of action. This can greatly reduce systemic exposure and potential side effects. In addition, mPEG-NH2 can be used not only to load small molecule drugs, but also to deliver biologics including proteins, peptides, and nucleic acids due to its easy modification and functionalization. The enhanced stability and solubility provided by mPEG-NH2 are critical for these larger, more complex drugs that are more susceptible to degradation and clearance. By improving the pharmacokinetic properties of biologics, mPEG-NH2 facilitates their clinical use, expanding the range of diseases that can be effectively treated with advanced drug delivery systems.
Alternate Names:
Methoxy polyethylene glycol amine
mPEG amine
Methoxy-PEG-amino compound
References:
1. He T, et al.; Modification strategies to improve the membrane hemocompatibility in extracorporeal membrane oxygenator (ECMO). Adv Compos Hybrid Mater. 2021, 4(4):847-864.
Nanoparticles-encapsulated doxorubicin alleviates drug resistance of osteosarcoma via inducing ferroptosis
Nanotoxicology
Authors: Tian X, Zhang Y, Zhang M, Liu G, Hao Y, Liu W.
Abstract
To determine the effects of polymeric nanoparticle for doxorubicin (Dox) delivery and treatment of drug-resistant Osteosarcoma (OS) cells. Methoxy-polyethylene glycol amino (mPEG-NH2) and platinum bio-mimetic polycaprolactone-cysteine (PtBMLC) were crosslinked to obtain glutathione (GSH)-responsive mPEG-NH2-PtBMLC polymer to encapsulate Dox (named as Nano-Dox). The particle size and zeta potential of the nanoparticles were measured, and internalization of Dox by OS cells was observed. After treatment with Nano-Dox, cell proliferation was determined by cell counting kit 8 (CCK-8) and colony formation assay. Cell migration and invasion were determined by Transwell assay. Cell cycle arrest was assessed by flow cytometry. The induction of ferroptosis was analyzed by abnormal accumulation of total iron, Fe2+. Nano-Dox exhibited a stronger localization in OS cells (p < 0.01). Nano-Dox induced more significant suppression of drug-resistant OS cell growth (p < 0.01), migration (p < 0.01), and invasion (p < 0.01), compared with the single Dox treatment group, along with decreased expression of N-cadherin, Snail, and Vimentin, suggesting impaired cancer migration and invasion. The treatment with Nano-Dox induced notable cell cycle arrest at G0/G1 phase (p < 0.01) and accumulation of iron, Fe2+, and MDA (p < 0.01), as well as suppressed the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11. Administration of ferroptosis inhibitor (Fer-1) reversed the anti-proliferation effects of Nano-Dox (p < 0.01). The Dox delivered by the polymeric nanoparticle system notably enhanced its effects on suppressing the growth, migration, and invasion of drug-resistant OS cells via inducing ferroptosis. The application of environment response polymer enhanced the delivery of Dox and the therapeutic effects on OS.
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