The Pursuit of Shortwave Infrared-Emitting Nanoparticles with Bright Fluorescence through Molecular Design and Excited-State Engineering of Molecular Aggregates

Abstract

Shortwave infrared (SWIR) fluorescence detection gradually becomes a pivotal real-time imaging modality, allowing one to elucidate biological complexity in deep tissues with subcellular resolution. The key challenge for the further growth of this imaging modality is the design of new brighter biocompatible fluorescent probes. This review summarizes the recent progress in the development of organic-based nanomaterials with an emphasis on new strategies that extend the fluorescence wavelength from the near-infrared to the SWIR spectral range and amplify the fluorescence brightness. We first introduce the most representative molecular design strategies to obtain near-infrared-SWIR wavelength fluorescence emission from small organic molecules. We then discuss how the formation of nanoparticles based on small organic molecules contributes to the improvement of fluorescence brightness and the shift of fluorescence to SWIR, with a special emphasis on the excited-state engineering of molecular probes in an aggregate state and spatial packing of the molecules in nanoparticles. We build our discussion based on a historical perspective on the photophysics of molecular aggregates. We extend this discussion to nanoparticles made of conjugated polymers and discuss how fluorescence characteristics could be improved by molecular design and chain conformation of the polymer molecules in nanoparticles. We conclude the article with future directions necessary to expand this imaging modality to wider bioimaging applications including single-particle deep tissue imaging. Issues related to the characterization of SWIR fluorophores, including fluorescence quantum yield unification, are also mentioned.

Structural design of conjugated polymers for fluorescence bioimaging in the second near‐infrared window

“…Cyclopentadithiophene, fluorene, and carbazole (Cz) are also used as the building blocks for the NIR-II fluorescent polymers of Pdot 20/21, Pdot 23/25, and Pdot 24, respectively (Figure 2). [69][70][71][72][73][74][75][76] These aromatic units have similar structures that are composed of the bithiophene or biphenyl bridged by an alkylsubstituted carbon or nitrogen atom to afford a fivemembered ring. The high planarity of these fused rings increases the degree of orbital overlap and electronic conjugation, resulting in red-shifted absorption and emission spectra.…”

“…72 The advantages of using the twisted Cz structure in the main chain backbone were comprehensively investigated by combining the experimental and computational studies. [73][74][75][76] TBZ has an alkyl side chain attached to the nitrogen atom, which makes it more soluble in monomers and their polymers than BBT. In addition, TBZ can adjust the electron affinity by changing the sulfur atom to another chalcogen atom (Se and Te), thus lowering the bandgaps and LUMO levels.…”

“…A similar tendency was observed for the twisted Cz‐based polymers with the BBT acceptor that display an NIR‐II emission (Figure 6C). 72 The advantages of using the twisted Cz structure in the main chain backbone were comprehensively investigated by combining the experimental and computational studies 73–76 …”

Investigation of near-infrared absorption properties by the GW–BSE method in heptamethine pyrylium dyes

“…16 In the ''cyanine limit'' configuration, the charge is fully delocalized over the entire conjugated backbone, as shown in Scheme 1, and cyanine dyes are able to produce sharp and intense absorption with a maximum absorption wavelength at the near-infrared (NIR) region (800-1500 nm). [17][18][19] The combination of the sharp and intense absorption properties with the influence of donor strength on the red-shift of the absorption wavelength makes cyanine dyes attractive for applications in bio-imaging or as photodynamic therapy agents under near-infrared radiation. 20,21 Cyanine dyes, with unique electronic properties of ''cyanine limit,'' pose a challenge in determining effective theoretical approaches to identifying the excited states.…”

Controlling AIE and ACQ properties of conjugated carbazole-tetraphenylethene copolymers by ethynylene spacer

“…[14][15][16] Polymer nanoparticles or polymer dots (Pdots) have been actively investigated as novel fluorescent probes in recent years because their fluorescent properties can be tuned by structural design. [17][18][19][20][21] A recent trend has focused on intense near-infrared (NIR) and the second near-infrared window (NIR-II) emissions that are suitable for bioimaging due to the biological window. 22 The excellent fluorescence brightness, photostability, and cytotoxicity of Pdots are expected to be applied to fluorescent tags 23,24 and biosensors.…”