Organic Fluorescent Dye-based Nanomaterials: Advances in the Rational Design for Imaging and Sensing Applications

Abstract

Self-assembled fluorescent nanomaterials based on small-molecule organic dyes are gaining increasing popularity in imaging and sensing applications over the past decade. This is primarily due to their ability to combine spectral properties tunability and biocompatibility of small molecule organic fluorophores with brightness, chemical and colloidal stability of inorganic materials. Such a unique combination of features comes with rich versatility of dye-based nanomaterials: from aggregates of small molecules to sophisticated core-shell nanoarchitectures involving hyperbranched polymers. Along with the ongoing discovery of new materials and better ways of their synthesis, it is very important to continue systematic studies of fundamental factors that regulate the key properties of fluorescent nanomaterials: their size, polydispersity, colloidal stability, chemical stability, absorption and emission maxima, biocompatibility, and interactions with biological interfaces. In this review, we focus on the systematic description of various types of organic fluorescent nanomaterials, approaches to their synthesis, and ways to optimize and control their characteristics. The discussion is built on examples from reports on recent advances in the design and applications of such materials. Conclusions made from this analysis allow a perspective on future development of fluorescent nanomaterials design for biomedical and related applications.

Keywords: Organic fluorophores; colloidal stability; molecular design; nanomaterial synthesis; polymeric aggregates; spectral properties; structure-property relationship; supramolecular assembly..

Fig. (1).

Number of publications mentioning fluorescent organic nanoparticles by year (based on data obtained from SciFinder).

Fig. (2).

Cyanine dyes and their expected assembly into micelles in the presence of non-coordinating ions (reproduced with permission from Shulov et al. [29] Copyright © The Royal Society of Chemistry, 2016).

Fig. (3).

(a) Chemical structures of amphiphiles and a photograph of a 0.3 μM nanoparticle solution under UV light (360 nm). (b)(i) Generation of nanoparticles prefunctionalized with mannose using mixtures of 1 and 2. (ii) Generation of nanoparticles prefunctionalized with azides using mixtures of 1 and 3 and their subsequent postfunctionalization via copper catalyzed azide-alkyne cycloaddition with alkyne derivatives of either mannose or biotin. (iii) Generation of bifunctional nanoparticles containing azides and mannose using mixtures of 2 and 3 and their subsequent postfunctionalization via copper catalyzed azide-alkyne cycloaddition with alkyne derived biotin yielding dual targeting mannose and biotin labeled nanoparticles (reproduced with permission from Petkau et al. [32] Copyright © American Chemical Society, 2011).

Fig. (4).

In vitro studies of depth detection and cellular uptake of self-assembled multimodal imaging nanoparticles. Fluorescence contrast in three different simulated tissue phantom models demonstrates viability as a contrast agent in a variety of tissue types, showing the contrast fluorescence image of tumor-like inclusions embedded into (a) adipose, (b) muscle and (c) liver tissue phantoms (adapted from Payne et al. [50] Copyright © William M. Payne et al., 2017).

Fig. (5).

Fluorescence changes from the photographs of TPE-BIMEG/ATP dispersions in the presence of various metal ions (1 mM) under a hand-held UV lamp illumination at 365 nm (reproduced with permission from Yang et al. [71]. Copyright © American Chemical Society, 2016).

Fig. (6).

(a) Proposed sensing mechanism for TPE-3 and biothiols. (b) Fluorescence spectra of TPE-3 (10 μM) upon addition of Cys (0–50 μM) in PBS buffer (10 mM, pH = 7.4, containing 45% DMSO). (c) Fluorescence response of TPE-3 at 589 nm to Cys concentration (0 – 50 μM). Inset: linear range for Cys detection. Spectra were recorded after incubation with different concentrations of Cys for 15 min, λ_ex = 370 nm. (d) Fluorescent photographs of TPE-3 deposited on test papers after immersed into buffer solutions (10 mM, pH = 7.4) with different concentrations of Cys under a UV lamp (365 nm) (reproduced with permission from Chen et al. [83] Copyright © The Royal Society of Chemistry, 2017).

Fig. (7).

Incubation duration-dependent confocal laser scanning microscopy images of live HepG2 cells when culturing with BP6 copolymer at 37 °C (adapted with permission from Hu et al. [88] Copyright © American Chemical Society, 2014).

Fig. (8).

Transmission electron microscopy images of HA-based NPs that were derived from 10 kDa or 100 kDa HA, using either PBA or 5βCA as hydrophobic substituents to drive self-assembly (scale bars = 100 nm). The subscript “100” or “10” refers to 100 or 10 kDa HA, respectively. “H”, “L”, and “Ø” refer to high, low, or no hydrophobic ligand conjugation to HA. (adapted from Hill et al. [48] Copyright © Ivyspring International Publisher, 2016).

Fig. (9).

A broad spectrum of factors, internal and external, affect the properties of fluorescent nanomaterials. Selecting an optimal combination of intrinsic properties of the components and the preparation procedure is of great importance for obtaining the nanomaterial with desired properties.