Single Nanoparticle SPR Imaging Measurements of Bioaffinity Uptake and Release in Polymer and DNA-Cross-linked Nanoparticles

University Of California-Irvine, Irvine CA

Investigators

Abstract

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Corn at the University of California, Irvine, is developing and applying new optical techniques that can detect, characterize and monitor in real time the size and composition of single polymer nanoparticles. Understanding how porous polymer nanoparticles uptake, transport, and then release biologically active molecules such as nucleic acids and proteins are fundamentally important and interesting. Professor Corn develops better chemical methods to improve the uniformity, reliability, and stability of characterization of these nanoparticles. Professor Corn's research outcome could lead to technological advances in the fields of sensor development, drug delivery, and disease diagnostics. Professor Corn's project provides participating students with research experience in a diverse set of disciplines: polymer materials and characterization, nanomaterials, laser microscopy, biosensors and biotechnology. Development of young scientists with such a wide range of skills is essential for both industry and academia to successfully address future multi-disciplinary technological challenges. In addition to research, this grant supports education and outreach programs that attract high school students from underfunded schools and middle school female students interested in science to the STEM fields. Single nanoparticle near-infrared surface plasmon resonance imaging (SPRI) microscopy is developed as a novel refractive index-based method to quantify the bioaffinity uptake and release of various biomolecules into individual porous polymeric nanoparticles. SPRI is an established refractive index-based technique for monitoring molecular and nanoparticle adsorption onto gold thin films. The application of SPRI microscopy is expanded here to single nanoparticle measurements that can monitor the uptake and release of biomolecules (both single nanoparticle averages and distribution measurements) in real time by measuring changes in the single nanoparticle refractive index that occur due to changes in composition. A variety of modified N-isopropylacrylamide (NIPAm) hydrogel nanoparticles that can uptake and release different proteins, lectins, nucleic acids, peptides, and pharmaceuticals are synthesized and studied. Three specific research efforts include: (i) the synthesis and characterization of NIPAm hydrogel nanoparticles that incorporate click chemistry sites to attach sugars, peptides, or DNA for the bioaffinity uptake and release of therapeutics, proteins, and RNA, (ii) the synthesis and characterization of DNA-cross-linked NIPAm (N-isopropylacrylamide)hydrogel nanoparticles that incorporate DNA aptamers and DNAzymes, and (iii) single-nanoparticle measurements of pH and temperature-induced morphological changes in NIPAm hydrogel nanoparticles that release various cargo (e.g., peptides, enzymes, DNA, and gold nanoparticles). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.