Scaleable production of long wavelength fluorescent nanoparticles to enable targeting and multiplexed imaging

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Long wavelength (NIR) fluorescent dyes enable deep tissue penetration and avoidance of tissue autofluorescence. In diagnostic applications and therapeutic drug delivery, targeting is often required. Nanoparticles offer advantages in targeted delivery because avidity of binding can be enhanced by presenting multiple copies of the targeting ligand on the nanoparticle surface. The combination of long wavelength fluorescence and targeting presents challenges in the production and scaleup of nanoparticles with repeatable and quantifiable characteristics. We present a novel technology-Flash NanoPrecipitation - a controlled precipitation process that produces stable nanoparticles at high concentrations of encapsulated components using amphiphilic block copolymers to direct self-assembly. Uniform particles with tunable sizes from 50 - 500 nm can be prepared in an economical, scalable, and reliable manner.[2] The key to the process is the control of time scales for micromixing, self-assembly, and nucleation and growth. Stoichiometric encapsulation of components enables the assembly of complex nanoparticles with tailored optical and targeting properties. Most bio-imaging, even for long wavelength dyes, has employed aqueous dyes that are conjugated onto the surfaces of nanoparticles. The long wavelength dyes are intrinsically large, conjugated structures and significant surface attachment may interfere with targeting. Instead we employ extremely hydrophobic dyes that remain sequestered in the cores. This enables higher loadings than are achievable with surface-attached dyes. Also, we show that several dyes which the community considers "hydrophobic" such as Nile red or ICG, partition out of nanoparticle cores to other lipid compartments and do not act as true reporters of the nanoparticle concentration or location. We report on two novel classes of NIR dyes: a hexacene based dye that has been first used in photo-voltaic applications, and a series of chlorin and bacteriochlorin dyes from Nirvana Sciences. The later dyes are particularly interesting because the wavelengths can be tuned at ∼10nm intervals over the NIR window as shown in Fig. 1. The native form of these dyes is hydrophobic, so they are ideally suited for encapsulation in our nanoparticle constructs. The narrow emission spectra will allow multiplexing of these dyes so that multiple populations of dyes with different targeting ligands can be injected simultaneously and their location/fate in vivo can be ascertained. We present targeting studies with these longwavelength dyes to show ligand density can be easily varied to determine optimum ligand concentration on the nanoparticle surface.[3].

Original languageEnglish (US)
Title of host publicationNanoscale Science and Engineering Forum 2015 - Core Programming Area at the 2015 AIChE Annual Meeting
PublisherAIChE
Pages370-373
Number of pages4
ISBN (Electronic)9781510818668
StatePublished - Jan 1 2015
EventNanoscale Science and Engineering Forum 2015 - Core Programming Area at the 2015 AIChE Annual Meeting - Salt Lake City, United States
Duration: Nov 8 2015Nov 13 2015

Publication series

NameNanoscale Science and Engineering Forum 2015 - Core Programming Area at the 2015 AIChE Annual Meeting

Other

OtherNanoscale Science and Engineering Forum 2015 - Core Programming Area at the 2015 AIChE Annual Meeting
CountryUnited States
CitySalt Lake City
Period11/8/1511/13/15

All Science Journal Classification (ASJC) codes

  • Chemical Engineering(all)
  • Environmental Engineering
  • Engineering(all)

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