Fluorescent Polymer Nanoparticles Based on Dyes: Seeking Brighter Tools for Bioimaging

Abstract

Speed, resolution and sensitivity of today's fluorescence bioimaging can be drastically improved by fluorescent nanoparticles (NPs) that are many-fold brighter than organic dyes and fluorescent proteins. While the field is currently dominated by inorganic NPs, notably quantum dots (QDs), fluorescent polymer NPs encapsulating large quantities of dyes (dye-loaded NPs) have emerged recently as an attractive alternative. These new nanomaterials, inspired from the fields of polymeric drug delivery vehicles and advanced fluorophores, can combine superior brightness with biodegradability and low toxicity. Here, we describe the strategies for synthesis of dye-loaded polymer NPs by emulsion polymerization and assembly of pre-formed polymers. Superior brightness requires strong dye loading without aggregation-caused quenching (ACQ). Only recently several strategies of dye design were proposed to overcome ACQ in polymer NPs: aggregation induced emission (AIE), dye modification with bulky side groups and use of bulky hydrophobic counterions. The resulting NPs now surpass the brightness of QDs by ≈10-fold for a comparable size, and have started reaching the level of the brightest conjugated polymer NPs. Other properties, notably photostability, color, blinking, as well as particle size and surface chemistry are also systematically analyzed. Finally, major and emerging applications of dye-loaded NPs for in vitro and in vivo imaging are reviewed.

Quantitative Assessment of Nanoparticle Biodistribution by Fluorescence Imaging, Revisited

“…However, the fluorescence intensity of dye-loaded NPs does not necessarily increase with the dye content in NPs. To the contrary, the concentrated dye molecules will face an increasing chance of aggregation-caused quenching 8,32 and appear darker in the imaging (Fig. 6).…”

“…6,7 In particular, organic NIR fluorophores, especially cyanine dyes, are most commonly used due to the flexibility in controlling absorption wavelength and emission brightness. 4,8 Representative NIR cyanine dyes include indocyanine green (ICG), a US Food and Drug Administration–approved dye, 9,10 and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR), a hydrophobic long-chain dialkylcarbocyanine. While both dyes can be physically encapsulated in NPs, ICG does not serve as a reliable probe of NPs as DiR in vivo .…”

Magnetic-Responsive Microparticles that Switch Shape at 37 °C

“…Polymeric micro/nano particles have enjoyed growing interest over the past several decades in drug delivery [1], optical bio-sensors [2], and bio-imaging [3]. In many of these applications, the ability to change chemical or physical properties in response to an external stimulus is greatly desired.…”

Stimulated Raman scattering of polymer nanoparticles for multiplexed live-cell imaging

“…Unfortunately, most polymeric nanoparticles rely on fluorescence reporting, and hence are limited by the intrinsic photophysics of fluorophores 15 , including self-quenching, broad emission, and photobleaching of organic dyes. Further compromising widespread use of polymer-based materials is the synthesis of complex architectures, such as bottle-brushes, star-shaped nanoparticles, and hollow nanomaterials 13 .…”