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Review
. 2019 Aug:94:44-63.
doi: 10.1016/j.actbio.2019.05.022. Epub 2019 May 11.

Quantum dots in biomedical applications

Angela M Wagner  1 , Jennifer M Knipe  1 , Gorka Orive  2 , Nicholas A Peppas  3
Affiliations
Review

Quantum dots in biomedical applications

Angela M Wagner et al. Acta Biomater. 2019 Aug.

Abstract

Semiconducting nanoparticles, more commonly known as quantum dots, possess unique size and shape dependent optoelectronic properties. In recent years, these unique properties have attracted much attention in the biomedical field to enable real-time tissue imaging (bioimaging), diagnostics, single molecule probes, and drug delivery, among many other areas. The optical properties of quantum dots can be tuned by size and composition, and their high brightness, resistance to photobleaching, multiplexing capacity, and high surface-to-volume ratio make them excellent candidates for intracellular tracking, diagnostics, in vivo imaging, and therapeutic delivery. We discuss recent advances and challenges in the molecular design of quantum dots are discussed, along with applications of quantum dots as drug delivery vehicles, theranostic agents, single molecule probes, and real-time in vivo deep tissue imaging agents. We present a detailed discussion of the biodistribution and toxicity of quantum dots, and highlight recent advances to improve long-term stability in biological buffers, increase quantum yield following bioconjugation, and improve clearance from the body. Last, we present an outlook on future challenges and strategies to further advance translation to clinical application. STATEMENT OF SIGNIFICANCE: Semiconducting nanoparticles, commonly known as quantum dots, possess unique size and shape dependent electrical and optical properties. In recent years, they have attracted much attention in biomedical imaging to enable diagnostics, single molecule probes, and real-time imaging of tumors. This review discusses recent advances and challenges in the design of quantum dots, and highlights how these strategies can further advance translation to clinical applications.

Keywords: Bioimaging; Drug delivery; Molecular probes; Nanotechnology; Theranostics.

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Figures

Figure 1.
Figure 1.
Illustrative structure of a CdSe quantum dot. Photon excitation causes electrons to move to a higher energy level, creating an electron-hole pair known as an exciton. If the electron and hole recombine as the electron returns to its ground state, fluorescence is emitted. Adapted from [41] with permission from Elsevier.
Figure 2.
Figure 2.
Optical properties of CdSe QDs (dispersed in chloroform) can be tuned by the size of the particle, known as the quantum size effect. (A) Fluorescence image of monodisperse QDs after ultraviolet illumination, ranging in size from 2.2 −7.3 nm. (B) Fluorescence spectra of the same four QD samples. Narrow and symmetric emission bands are observed, indicating low variance in particle size. (C) Absorption spectra of the same four QD samples. Broad absorption spectra are observed, enabling a wide range for excitation of the QDs. Adapted from [9] with permission from Elsevier.
Figure 3.
Figure 3.
Schematic depicting the synthesis of a QD and the addition of a passivating layer, resulting in a “core-shell” structure. Typical reagents reported in current literature are shown. Adapted from [10] with permission from Elsevier.
Figure 4.
Figure 4.
Polymer encapsulation of a CdSe QD. The polymer is a functionalized amphiphilic anhydride, where R represents a functional group (R= -NH2, -OH, etc.). The hydrophobic ligands interact with the hydrophobic regions of the amphiphile, creating a polymer micelle with colloidal stability and solubility in water. Adapted from [43] with permission from Springer Nature.
Figure 5.
Figure 5.
(A) General structure of DHLA-TEG-quaternary ammonium cationic ligand, where R represents a functional group. (B) Two-step ligand exchange scheme. Step 1: Hydrophobic QDs are converted to amphiphilic QDs by exchange with DHLA capped tetra(ethylene glycol) (TEG) chains. Step 2: Addition of the quaternary ammonium terminus, resulting in hydrophilic, cationic QDs. Adapted from [57] with permission from the Royal Society of Chemistry.
Figure 6.
Figure 6.
Conjugation of the QD surface with biomolecules depends heavily upon the ligand chemistries available to provide suitable functional groups for covalent attachment or noncovalent binding. (A) Illustration of phase transfer followed by EDC/NHS carbodiimide chemistry to conjugate a CdSe/ZnS quantum dot with antibody [74]. (B) Schematic of antibody conjugated QD synthesis using copper free cycloaddition ‘click’ chemistry [221]. Figures adapted from [74] with permission from Elsevier, and [221] with permission from the American Chemical Society.
Figure 7.
Figure 7.
Real-time in vivo imaging of non-targeted versus targeted QD biodistribution in a nude mouse model 24 hours after intravenous injection of QDs. Fluorescence intensity reflects accumulation of QDs; blue represents lowest intensity and red represents highest. Targeted QDs showed greater accumulation at the tumor site than non-targeted QDs. Adapted from [60] with permission from Elsevier.
Figure 8.
Figure 8.
Cd/Se core-Zn/S shell QD/siRNA complexes enable sorting of transfected cell populations. (A) A schematic representing the transfection of fibroblast cells with liposome/siRNA/QD complexes. Fluorescence was measured using flow cytometry, and the histograms show control cells, siRNA-treated cells, and QD/siRNA-treated cells. (B) Western blot of Lamin A/C expression after transfection (β-actin as loading control). Cells with a high level siRNA/QD fluorescence show knockdown of the Lamin genes. (C) Band densitometry analysis of the western blots. Adapted from [215] with permission from Oxford University Press.
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