Elsevier

Progress in Polymer Science

Volume 39, Issue 2, February 2014, Pages 365-395
Progress in Polymer Science

Design and development of fluorescent nanostructures for bioimaging

https://doi.org/10.1016/j.progpolymsci.2013.11.001Get rights and content

Abstract

Because fluorescence-based techniques are inherently sensitive, selective, convenient, diverse, non-destructive, potentially real time and in situ, they have been widely used in biological imaging. Especially those, with specific fluorescent nanostructures (FNSs) as detecting media in bioimaging, have already been intensively studied for more than a decade because of the convenient transduction of optical signal, high sensitivity and rapid response of FNSs. In this review, we summarize the major strategies to design FNSs with specific structures for biological imaging. First, recent advances are briefly introduced. Then, the specific design of FNSs and their applications are reviewed, in which their fluorescence mechanism, strategies in designing and development, preparation methods, and some representative applications in bioimaging are described. Finally, future perspectives and ongoing issues of FNSs and their applications in bioimaging are discussed. Although many FNSs have been synthesized and applied biologically, many studies still should be done before they can be widely employed as fluorescent probes in clinical tests. With further advances in design and synthesis of high quality multifunctional FNSs, the widespread application of FNSs may be expected not only in advanced bioimaging, but also in ultra-sensitive molecular diagnosis, novel light-emitting nanodevices and intracellular drug delivery.

Introduction

Biological imaging (bioimaging) has become a powerful tool in biological research today because it offers an unique approach to visualize the morphological details of cells [1]. To date, fluorescence-based techniques have been greatly encouraged in bioimaging due to their inherent superiorities, such as high sensitivity, high selectivity, convenience, diversity and non-destructive character [2]. Typically, fluorescent probes are exploited to label the target with specific chemical structures and thus to generate fluorescent signals during the fluorescence-based bioimaging. Since nanostructure-based detection platforms can provide many advantages over traditional approaches in terms of sensitivity, signal stability and multiplexing capability, a growing interest has been shown recently in the design of different fluorescent nanostructures (FNSs) as fluorescent probes in bioimaging [3], [4], [5], [6]. Currently, the most studied FNSs in bioimaging include fluorescent proteins, organic dyes, metal complexes, semiconductor nanocrystals, and upconversion nanophosphors [7], [8], [9], [10]. In order to obtain a better fluorescent probe, further works on FNSs with recommended chemical and optical properties have also been reported. For example, surface modification of FNSs has been done with bright fluorescence, high photostability, large Stokes shift and flexible processability in order to be further conjugated with biomolecules and/or fluorophores [6].

In this review, classification of FNSs, their fluorescence mechanisms and applications in bioimaging are summarized. According to the compositions and structures of FNSs, they are divided into three classifications, i.e., organic FNSs, inorganic FNSs and organic/inorganic hybrid FNSs (Fig. 1). Based on the classification of FNSs, their design strategies, fluorescing mechanisms, size-dependent optical properties and preparing methods are introduced and discussed. Especially, their representative applications in bioimaging at the cell- and tissue-levels are reviewed. Furthermore, potentials of FNSs and their perspectives in the field of bioimaging, based on their advantages and security, are discussed.

Section snippets

Organic fluorescent nanostructures

Among all of the FNSs used in bioimaging, organic FNSs are the most widely studied due to their rich chemical structures, easy chemical modification and high fluorescence quantum yield (FQY) [11], [12]. Generally, these organic FNSs include carbon-based fluorescent nanostructures, fluorescent macromolecules, fluorescent polymeric nanoparticles, fluorescent supermacromolecular nanoassemblies and aggregation-induced emission fluorophores.

Inorganic fluorescent nanostructures

Inorganic FNSs are usually nanoclusters (NCs) or NPs with great potential advantages in bioimaging because of their interesting self-fluorescent properties. It was well known that, with very few exceptions, fluorescent lifetimes of organic dyes are too short (1–10 ns) for efficient temporal discrimination of short-lived fluorescence interference from scattered excitation light. Comparatively, inorganic FNSs have longer lifetimes (typically five to hundreds of nanoseconds) [192], which makes them

Organic/inorganic hybrid fluorescent nanostructures

With rational design, combining multiple constituents into a single nanoobject will not only bridge the unique properties of individual sections, but also improve conventional sensing, imaging, and therapeutic efficacies. To improve the application in bioimaging, FNSs are usually designed as organic/inorganic hybrid compositions. The core and shell segments alternately contributed to the desired fluorescent properties or acted as protecting agents of matrix or scaffold, which thus offers better

Perspective

Due to their attractive properties, including ultrasmall size, high brightness, monodispersity and low photobleaching, FNSs represent a highly attractive platform for bioimaging [328]. Despite their great potential and promising future as novel fluorescent probes in bioimaging, further improvement of FNSs still faces many challenges.

First, progress in the design and development of better synthesis routes for different FNSs with good target specifity are needed. The required selectivity, e.g.,

Summary

We summarize the extensive efforts on the development of FNSs, which have attractive features for their applications in bioimaging. In this review, we first introduce three classifications of bioimaging FNSs according to their chemical compositions. Their specific structural designs, synthetic strategies and the size effects on the optical properties are subsequently summarized. Great efforts have been made to improve their fluorescence intensity, specificity in targeting, biocompatibility and

Acknowledgements

The authors acknowledge the financial support of the “National Science Foundation of China” (21174012, 51103008, 51221002) and the “New Century Excellent Talents Award Program, Ministry of Education, China (NCET-10-0215)” and the Doctoral Program of Higher Education Research Fund (20100010120006, 20120010110008).

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