Background
Magnetofluorescent nanoparticles have come more and more into the spotlight recently for their many applications in biomedical detection and application of area-specific drugs. Most conventional nanoparticles are coated with anti-fouling polyethylene glycol (PEG) in order to achieve the required bio-availability and biocompatibility. However, PEGs are sensitive to solution pH and tend to cause nanoparticles to aggregate in acidic or salt-rich microenvironments. This aggregation can further degrade or even change the diagnosis/therapy functionalities of the original nanoparticles. This understandably limits their applications in biomedical applications, which almost always occur in harsher environments.
Description
Starting with poly(maleic anhydride-alt-1-octadecene) (PMAO polymers) researchers at the University Of Nevada, Reno converted anhydride rings in polymers to the desired zwitterionic group, thus modifying the PMAO polymers to zwitterionic amphiphiles. Utilizing these, researchers were able to apply the zwitterionic amphiphile coating to magnetofluorescent nanoparticles (ZW-MFNPs), which can now be used safely in many biomedical applications.
Advantages
- Excellent stability in aqueous solutions with a wide pH/ionic-strength range and physiological media
- Low cytotoxicity
- Bioconjugation capability for specific biomolecular binding
- Able to overcome the limitations of PEGs for nanoparticle applications
Patent
US10994031B2
PCT/US2016/042613
15/872,763
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UNR15-023