Synthesis of amphiphilic triblock copolymers as multidentate ligands for biocompatible coating of quantum dots

Abstract

One barrier to apply current tri-octylphosphine oxide (TOPO) based quantum dots (QDs) to biomedical imaging is that the TOPO on TOPO-QDs can be replaced by the proteins in living system, which may cause the degradation of QDs and/or deactivation of protein. In order to develop biocompatible optical imaging agents, a novel triblock copolymer, designed as a multidentate ligand, was synthesized to coat quantum dot nanocrystals (QDs). The copolymer consists of a polycarboxylic acid block at one end and a polythiol block at the other end with an intervening cross-linked poly(styrene-co-divinylbenzene) block bridging the ends. The multiple mercapto groups from the polythiol block act as multidentate ligands to stabilize QDs, while the polycarboxylic acid block improves the water solubility of QDs and offers reaction sites for surface modification or conjugation with bimolecules. The cross-linked poly(styrene-co-divinylbenzene) block provides a densely compacted hydrophobic shell. This shell will act as a barrier to inhibit the degradation of QDs by preventing the diffusion of ions and small molecules into the core of QDs. This new multidentate polymer coating facilitates the transfer of QDs from organic solvent into aqueous phase. The QDs directly bound to multidentate mercapto groups instead of TOPO are less likely to be affected by the mercapto or disulfide groups within proteins or other biomolecules. Therefore, this research will provide an alternative coating material instead of TOPO to produce QDs which could be more suitable for in vivo use under complex physiological conditions.

Techniques for physicochemical characterization of nanomaterials

“…The strong signal generated by the nanomaterial-based contrast agents, in fact, helps overcome the essential disadvantages of low sensitivity in MRI and limited depth penetration of optical imaging to a certain degree (Lam et al, 2013; Rosenblum et al, 2010; Thomas et al, 2013). Given the novel properties of nanomaterials, several distinct nanomaterials are commonly designed as nanoscale imaging probes, including quantum dots with specific electronic and optical properties, upconversion phosphors consisting of phosphor nanocrystals doped with rare earth metals, and super-paramagnetic iron oxide particles containing an iron oxide core of magnetite and/or maghemite encased in polysaccharide, synthetic polymer or monomer coatings, or other soft materials like dendrimers (Biju et al, 2010a; Liang et al, 2008; Rosenblum et al, 2010; Wang et al, 2011). In addition to the characteristics of conventional imaging probes, such as structure, purity and solubility, certain physicochemical properties of nanomaterial-based imaging contrast agents also have to be considered, including size, shape, composition, zeta potential and dispersion (Leung et al, 2012).…”

Acetyl protected thiol methacrylic polymers as effective ligands to keep quantum dots in luminescent standby mode

“…The coating of QDs can be done using polymeric materials, which offer some important advantages, such as a decrease of toxicity, an increasing of the long-term stability and, very importantly, the polymers endow the QDs with new physicochemical properties. [7][8][9] During the last years, several strategies have been developed with this purpose, some of them include the encapsulation with amphiphilic polymers [9][10][11] and phospholipic micelles. 12 The main disadvantage of these procedures is the increase of size of the QD nanostructure, which is undesirable for some applications.…”

Surface functionalization of quantum dots for biological applications

“…The target specific delivery of quantum dots is essential to minimize their exposure to non-relevant cells, increase greater contrast and localized application of FRET based processes [4,58]. The strategies for bio-functionalization revolve around the two main anchor points -the native thiol bonding between the sulphur groups from ZnS capped QDs and the bi-functional thiol ligands or silanes [28] and like hydrophobic interaction between the hydrophobic ligands from QDs and hydrophobic end from block co-polymers [61]. , Phase transfer and particle functionalization, have served as the two most common strategies for QDs surface modification with biomolecules, linkers used and the processes involved ( Table 2).…”