Biocompatible polymer/quantum dots hybrid materials: current status and future developments

Abstract

Quantum dots (QDs) are nanometer-sized semiconductor particles with tunable fluorescent optical property that can be adjusted by their chemical composition, size, or shape. In the past 10 years, they have been demonstrated as a powerful fluorescence tool for biological and biomedical applications, such as diagnostics, biosensing and biolabeling. QDs with high fluorescence quantum yield and optical stability are usually synthesized in organic solvents. In aqueous solution, however, their metallic toxicity, non-dissolubility and photo-luminescence instability prevent the direct utility of QDs in biological media. Polymers are widely used to cover and coat QDs for fabricating biocompatible QDs. Such hybrid materials can provide solubility and robust colloidal and optical stability in water. At the same time, polymers can carry ionic or reactive functional groups for incorporation into the end-use application of QDs, such as receptor targeting and cell attachment. This review provides an overview of the recent development of methods for generating biocompatible polymer/QDs hybrid materials with desirable properties. Polymers with different architectures, such as homo- and co-polymer, hyperbranched polymer, and polymeric nanogel, have been used to anchor and protect QDs. The resulted biocompatible polymer/QDs hybrid materials show successful applications in the fields of bioimaging and biosensing. While considerable progress has been made in the design of biocompatible polymer/QDs materials, the research challenges and future developments in this area should affect the technologies of biomaterials and biosensors and result in even better biocompatible polymer/QDs hybrid materials.

Figure 1

A schematic depiction of polymer/QDs hybrids. Biocompatible polymers protect QDs as shells providing biocompatibility and biostability and, at the same time, introduce functional groups for targeting cell and biomolecules.

Figure 2

Schematic summary of synthetic strategies for fabricating biocompatible polymer/QDs hybrid materials, which can be categorized into (A) ligand exchange between polymer and QDs; (B) grafting polymer to QDs; (C) grafting polymer from QDs; (D) capping polymer onto QDs; and (E) growing QDs within polymeric template.

Figure 3

Chemical structures of biocompatible polymers employed for the fabrication of polymer/QDs hybrid materials described in this review.

Figure 4

A schematic representation of ligand exchange process of poly(2-(dimethy-lamino)ethyl methacrylate) (PDMAEMA) with CdSe QDs, where the polymer binds to QDs in the form of small loops. 3% of PDMAEMA chain interacts directly with QDs as train structures and 97% is present in form of loops and tails protruding into solution. Reprinted with permission from reference [17].

Figure 5

Single PSS/PAL/Gold nanoparticle through layer-by-layer capping method. Below are transmission electron micrographs of hybrid nanoparticles with different number of PSS/PAL layers. Reprinted with permission from reference [56].

Figure 6

PEG/CdSe QDs labeling of Xenopus embryos at different stages. (A) Schematic showing the experimental strategy; (B) Injection of one cell out of an eight-cell-stage embryo resulted in labeling of individual blastomeres; (C) Same embryo shown 1 h later; The daughter cells of the injected blastomere are labeled (D) and at a later stage (E) show two neurula embryos, which were injected into single cell at the eight-cell-stage in the animal pole. Reproduced with permission from ref .

Figure 7

Spectral imaging of QD-PSMA Ab conjugates in live animals harboring C4-2 tumor xenografts. Orange-red fluorescence signals indicate a prostate tumor growing in a live mouse (right). Control studies using a healthy mouse (no tumor) and the same amount of QD injection showed no localized fluorescence signals (left). (A) Original image; (B) unmixed autofluorescence image; (C) unmixed QD image; and (D) super-imposed image. After in vivo imaging, histological and immunocytochemical examinations confirmed that the QD signals came from an underlying tumor. Note that QDs in deep organs such as liver and spleen were not detected because of the limited penetration depth of visible light. Reproduced with permission from Reference [41].

Figure 8

Polymer nanosphere/QDs hybrids. (A) Dark-field TEM image of one hybrid poly(N-vinylcaprolactam)/Lanthanide QDs (PVCL/La) particle. (B) Laser confocal fluorescence microscopy (LCFM) image of THP-1 cells labeled by PVCL/La. Reproduced with permission from Reference [67].

Figure 9

A schematic structure of a single-polymer/QDs-based biosensor in the presence of acceptor molecule with fluorescence emission at 670 nm and illumination on QDs cased by fluorescence resonance energy transfer (FRET) between acceptor molecule and QDs donor. Polymer introduces functional groups for targeting the acceptor molecules.