In the realm of drug delivery systems, the development of biocompatible and effective carriers is paramount for enhancing the therapeutic efficacy and reducing the side effects of pharmaceuticals. One such promising compound is OPSS-PEG-NH2, which stands for ortho-pyridyl disulfide poly(ethylene glycol) amine. This multifunctional molecule combines the advantageous properties of polyethylene glycol (PEG) with the reactivity of ortho-pyridyl disulfide and the functional versatility of an amine group. OPSS-PEG-NH2 is gaining significant attention in the pharmaceutical and biomedical fields due to its potential to form stable conjugates with a variety of therapeutic agents, thus improving their solubility, stability, and bioavailability. The core of OPSS-PEG-NH2 is PEG, a polymer known for its excellent biocompatibility and ability to extend the circulation time of drugs in the bloodstream by evading the immune system. PEGylation, the process of attaching PEG chains to molecules, has been a well-established strategy in drug delivery to reduce immunogenicity and enhance the pharmacokinetic profiles of therapeutic agents. The addition of the ortho-pyridyl disulfide (OPSS) group introduces a unique thiol-reactive moiety, which enables the formation of covalent bonds with thiol-containing molecules through a disulfide exchange reaction. This capability is particularly valuable for creating stable drug conjugates that can release their payload in a controlled manner, especially in the reductive environment of cancer cells or inflamed tissues where higher concentrations of glutathione can cleave the disulfide bond. Furthermore, the amine group in OPSS-PEG-NH2 offers additional functionalization opportunities, allowing for the attachment of various targeting ligands, fluorescent markers, or therapeutic agents through conventional amide bond formation. This versatility makes OPSS-PEG-NH2 a powerful tool for the design of targeted drug delivery systems. By conjugating targeting ligands such as antibodies, peptides, or small molecules, OPSS-PEG-NH2 can facilitate the precise delivery of drugs to specific cells or tissues, thereby maximizing therapeutic efficacy and minimizing off-target effects. Moreover, the inclusion of fluorescent markers can aid in the real-time tracking and imaging of drug delivery and distribution, providing valuable insights into the biodistribution and therapeutic outcomes of the conjugated drugs.
Figure 1. Labeling of gold nanoshells by bifunctional OPSS-PEG-NHS and DOTA-NH2. (Xie H, et al.; 2012)
The design of drug delivery systems using OPSS-PEG-NH2 is highly adaptable to various therapeutic needs. For example, in cancer therapy, targeting ligands such as monoclonal antibodies can be attached to OPSS-PEG-NH2 to direct chemotherapeutic agents specifically to tumor cells, sparing healthy tissue and reducing systemic toxicity. This targeted approach not only improves the therapeutic index of the drugs but also enhances patient outcomes by minimizing adverse side effects. Similarly, in gene therapy, OPSS-PEG-NH2 can be used to deliver nucleic acids such as siRNA or plasmid DNA to specific cells, improving the efficiency of gene silencing or expression while reducing off-target effects.In addition to targeting capabilities, the ability of OPSS-PEG-NH2 to improve drug solubility and stability is crucial for the development of effective drug formulations. Many therapeutic agents, especially small-molecule drugs, suffer from poor water solubility, which limits their bioavailability and therapeutic efficacy. By conjugating these drugs to OPSS-PEG-NH2, their solubility can be significantly enhanced, facilitating their delivery and absorption in the body. Moreover, the PEG component helps to protect the drug from enzymatic degradation and clearance by the immune system, further extending its circulation time and therapeutic effect. The role of OPSS-PEG-NH2 in improving the pharmacokinetic properties of drugs is complemented by its potential to enable controlled drug release. The disulfide bond formed between OPSS-PEG-NH2 and thiol-containing drugs is stable under normal physiological conditions but can be cleaved in the presence of high concentrations of reducing agents such as glutathione, which are often found in the intracellular environment of cancer cells. This allows for the release of the drug specifically at the target site, reducing systemic exposure and enhancing the therapeutic effect. This controlled release mechanism is particularly beneficial in the treatment of diseases such as cancer, where precise delivery and release of the therapeutic agent are critical for achieving optimal therapeutic outcomes.
Another significant advantage of OPSS-PEG-NH2 is its biocompatibility and minimal immunogenicity. PEGylation is known to reduce the recognition and clearance of therapeutic agents by the immune system, thereby prolonging their circulation time and enhancing their bioavailability. This property is particularly important for the repeated administration of therapeutic agents, as it helps to reduce the risk of immune responses and adverse reactions. Additionally, the biocompatibility of PEG ensures that OPSS-PEG-NH2-based drug delivery systems are well-tolerated by the body, reducing the risk of toxicity and other side effects. The versatility of OPSS-PEG-NH2 extends to its applications beyond traditional drug delivery. For instance, it can be used in the development of diagnostic agents and imaging probes. By conjugating OPSS-PEG-NH2 with fluorescent markers or contrast agents, it is possible to create multifunctional probes that can be used for both therapeutic and diagnostic purposes, a concept known as theranostics. These probes can be used to monitor the delivery and distribution of drugs in real-time, providing valuable information on the biodistribution and therapeutic efficacy of the treatment. This dual functionality is particularly useful in personalized medicine, where tailored treatment strategies are developed based on the specific needs and conditions of individual patients.
Alternate Names:
Oligo(ethylene glycol) propyl sulfide-PEG-amine
PEGylated OPSS amine
OPSS-PEG amino compound
References:
1. Xie H, et al.; Effect of intratumoral administration on biodistribution of 64Cu-labeled nanoshells. Int J Nanomedicine. 2012, 7:2227-38.
Synthesis of SERS-active core-satellite nanoparticles using heterobifunctional PEG linkers
Nanoscale Adv.
Authors: San Juan AMT, Chavva SR, Tu D, Tircuit M, Coté G, Mabbott S.
Abstract
Surface-enhanced Raman scattering (SERS) is a sensitive analytical technique capable of magnifying the vibrational intensity of molecules adsorbed onto the surface of metallic nanostructures. Various solution-based SERS-active metallic nanostructures have been designed to generate substantial SERS signal enhancements. However, most of these SERS substrates rely on the chemical aggregation of metallic nanostructures to create strong signals. While this can induce high SERS intensities through plasmonic coupling, most chemically aggregated assemblies suffer from poor signal reproducibility and reduced long-term stability. To overcome these issues, here we report for the first time the synthesis of gold core-satellite nanoparticles (CSNPs) for robust SERS signal generation. The novel CSNP assemblies consist of a 30 nm spherical gold core linked to 18 nm satellite particles via linear heterobifunctional thiol-amine terminated PEG chains. We explore the effects that the varying chain lengths have on SERS hot-spot generation, signal reproducibility and long-term activity. The chain length was varied by using PEGs with different molecular weights (1000 Da, 2000 Da, and 3500 Da). The CSNPs were characterized via UV-Vis spectrophotometry, transmission electron microscopy (TEM), ζ-potential measurements, and lastly SERS measurements. The versatility of the synthesized SERS-active CSNPs was revealed through characterization of optical stability and SERS enhancement at 0, 1, 3, 5, 7 and 14 days.
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