Semiconductor quantum dots (QDs) have become important fluorescent probes for in vitro and in vivo bioimaging research. Their nanoparticle surfaces for versatile bioconjugation, their adaptable photophysical properties for multiplexed detection, and their superior stability for longer investigation times are the main advantages of QDs compared to other fluorescence imaging agents. Here, we review the recent literature dealing with the design and application of QD-bioconjugates for advanced in vitro and in vivo imaging. After a short summary of QD preparation and their most important properties, different QD-based imaging applications will be discussed from the technological and the biological point of view, ranging from super-resolution microscopy and single-particle tracking over in vitro cell and tissue imaging to in vivo investigations. A substantial part of the review will focus on multifunctional applications, in which the QD fluorescence is combined with drug or gene delivery towards theranostic approaches or with complementary technologies for multimodal imaging. We also briefly discuss QD toxicity issues and give a short outlook on future directions of QD-based bioimaging.

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Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors

Graphene is composed of single-atom thick sheets of sp2 bonded carbon atoms that are arranged in a perfect two-dimensional (2D) honeycomb lattice. Because of this structure, graphene is characterized by a number of unique and exceptional structural, optical, and electronic properties.1 Specifically, these extraordinary properties include, but are not limited to, a high planar surface area that is calculated to be 2630 m2 g−1,2 superior mechanical strength with a Young’s modulus of 1100 GPa,3 unparalleled thermal conductivity (5000 W m−1 K−1),4 remarkable electronic properties (e.g., high carrier mobility [10 000 cm2 V−1 s−1] and capacity),5 and alluring optical characteristics (e.g., high opacity [~97.7%] and the ability to quench fluorescence).6 As such, it should come as no surprise that graphene is currently, without any doubt, the most intensively studied material for a wide range of applications that include electronic, energy, and sensing outlets.1c Moreover, because of these unique chemical and physical properties, graphene and graphene-based nanomaterials have attracted increasing interest, and, arguably, hold the greatest promise for implementation into a wide array of bioapplications.7

In the last several years, numerous studies have utilized graphene in bioapplications ranging from the delivery of chemotherapeutics for the treatment of cancer8 to biosensing applications for a host of medical conditions9 and even for the differentiation and imaging of stem cells.10 While promising and exciting, recent reports have demonstrated that the combination of graphene with nanomaterials such as nanoparticles, thereby forming graphene–nanoparticle hybrid structures, offers a number of additional unique physicochemical properties and functions that are both highly desirable and markedly advantageous for bioapplications when compared to the use of either material alone (Figure 1).11 These graphene–nanoparticle hybrid structures are especially alluring because not only do they display the individual properties of the nanoparticles, which can already possess beneficial optical, electronic, magnetic, and structural properties that are unavailable in bulk materials, and of graphene, but they also exhibit additional advantageous and often synergistic properties that greatly augment their potential for bioapplications.




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Figure 1


Graphene nanoparticle hybrids exist in two forms, as graphene–nanoparticle composites and graphene-encapsulated nanoparticles, and can be used for various bioapplications including biosensors, photothermal therapies, stem cell/tissue engineering, drug/gene delivery, and bioimaging. Panel (A) reprinted with permission from ref 110. Copyright 2012 Wiley. Panel (B) reprinted with permission from ref 211. Copyright 2013 Elsevier. Panel (C) reprinted with permission from ref 244. Copyright 2013 Wiley.

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Design, Synthesis, and Characterization of Graphene–Nanoparticle Hybrid Materials for Bioapplications

Biosynthesis and Bioconjugation to Biomedical Application Juan Zhou,‡,§ Yong Yang, and Chun-yang Zhang*,†,§ †College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, China ‡State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China Single-Molecule Detection and Imaging Laboratory, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

Toward Biocompatible Semiconductor Quantum Dots: From Biosynthesis and Bioconjugation to Biomedical Application

Carbon nanotubes for delivery of small molecule drugs

Photoluminescent graphene quantum dots (GQDs) have fascinating optical and electronic properties with numerous promising applications in biomedical engineering. In this work, we first studied the in vivo biodistribution and the potential toxicity of carboxylated photoluminescent GQDs. KB, MDA-MB231, A549 cancer cells, and MDCK normal cell line were chosen as in vitro cell culture models to examine the possible adverse effects of the carboxylated photoluminescent GQDs. The carboxylated GQDs are desirable for increased aqueous solubility. All cancer cells efficiently took up the carboxylated GQDs. No acute toxicity or morphological changes were noted in either system at the tested exposure levels. A long-term in vivo study revealed that the GQDs mainly accumulated in liver, spleen, lung, kidney, and tumor sites after intravenous injection. To reveal any potential toxic effect of the GQDs on treated mice, serum biochemical analysis and histological evaluation were performed. The toxicity results from serum b...

In Vivo Biodistribution and Toxicology of Carboxylated Graphene Quantum Dots

Quantum-Dot-Conjugated Graphene as a Probe for Simultaneous Cancer-Targeted Fluorescent Imaging, Tracking, and Monitoring Drug Delivery

A novel and specific nanoplatform for in vitro simultaneous cancer-targeted optical imaging and magnetically guided drug delivery is developed by conjugating CdTe quantum dots with Fe(3)O(4)-filled carbon nanotubes (CNTs) for the first time. Fe(3)O(4) is filled into the interior of the CNTs, which facilitates magnetically guided delivery and improves the synergetic targeting efficiency. In comparison with that immobilized on the external surface of CNTs, the magnetite nanocrystals inside the CNTs protect it from agglomeration, enhance its chemical stability, and improve the drug loading capacity. It also avoids magnetic nanocrystals-induced quenching of fluorescence of the quantum dots. The SiO(2)-coated quantum dots (HQDs) attached on the surface of CNTs exhibit favorable fluorescence as the hybrid SiO(2) shells on the QDs surface prevent its fluorescence quenching caused by the CNTs. In addition, the hybrid SiO(2) shells also mitigate the toxicity of the CdTe QDs. By coating transferrin on the surface of the herein modified CNTs, it provides a dual-targeted drug delivery system to transport the doxorubicin hydrochloride (DOX) into Hela cells by means of an external magnetic field. The nanocarrier based on the multifunctional nanoplatform exhibits an excellent drug loading capability of ca. 110%, in addition to cancer-targeted optical imaging as well as magnetically guided drug delivery.

Ye-Ju He

Papers

Quantum-Dot-Conjugated Graphene as a Probe for Simultaneous Cancer-Targeted Fluorescent Imaging, Tracking, and Monitoring Drug Delivery

Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancer-targeted imaging and magnetically guided drug delivery.