Three bisphosphonate ligands improve the water solubility of quantum dots

Abstract

Synthesised Quantum Dots (QDs) require surface modification in order to improve their aqueous dispersion and biocompatibility. Here, we suggest bisphosphonate molecules as agents to modify the surface of QDs for improved water solubility and biocompatibility. QDs_TOPO (CdSe/ZnS-trioctylphosphine oxide) were synthesised following modification of the method of Bawendi et al. (J. Phys. Chem. B, 1997, 101, 9463-9475). QDs surface modification is performed using a ligand exchange reaction with structurally different bisphosphonates (BIPs). The BIPs used were ethylene diphosphonate (EDP), methylenediphosphonate (MDP) and imidodiphosphonate (IDP). After ligand exchange, the QDs were extensively purified using centrifugation, PD-10 desalting columns and mini dialysis filters. Transmission electron microscopy (TEM) and fluorescent spectroscopy have been used to characterise the size and optical properties of the QDs. Cell toxicity was investigated using MTT (tetrazolium salt) and glutathione assays and intracellular uptake was imaged using confocal laser scanning microscopy and assessed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). QDs_TOPO and QDs-capped with BIPs (QDs_BIPs) were successfully synthesised. TEM showed the size and morphology of the QDs to be 5-7 nm with spherical shape. The stabilised QDs_BIPs showed significantly improved dispersion in aqueous solutions compared to QDs_TOPO. The cytotoxicity studies showed very rapid cell death for cells treated by QDs_TOPO and a minor effect on cell viability when QDs_BIPs were applied to the cells. Both EDP- and MDP-modified QDs did not significantly increase the intracellular levels of glutathione. In contrast, IDP-modified QDs substantially increased the intracellular glutathione levels, indicating potential cadmium leakage and inability of IDP to adequately cap and stabilise the QDs. EDP- and MDP-modified QDs were taken up by IGROV-1 (ovarian cancer) cells as shown by fluorescence microscopy, however, the IDP-modified QD signal was not clearly visible in the cells. Cellular uptake measured by intracellular cadmium levels using ICP-MS showed significant uptake of all three BIPs QDs. The structure of BIPs appears to play a significant role in the ability of these molecules to act as capping agents. Our findings demonstrate a novel approach to produce water-dispersible QDs through ligand exchange with certain types of BIPs molecules that can find application in bioimaging.

Current Advances in the Biomedical Applications of Quantum Dots: Promises and Challenges

“…For example, Ghani et al, replaced the original hydrophobic tri-octyl phosphine oxide (TOPO) ligands on CdSe/ZnS QDs with different types of water-soluble bisphosphonate (BIP)-based ligands, such as ethylene diphosphonate (EDP), imido diphosphonate (IDP), and methylene diphosphonate (MDP). The results showed that the exchanged ligand improved the water solubility and dispersal of CdSe/ZnS QDs [ 22 ]. Furthermore, EDP-, IDP-, and MDP-conjugated CdSe/ZnS QDs were shown to have lower toxicity effects compared to CdSe/ZnS QDs conjugated with TOPO ligands.…”

“…Furthermore, EDP-, IDP-, and MDP-conjugated CdSe/ZnS QDs were shown to have lower toxicity effects compared to CdSe/ZnS QDs conjugated with TOPO ligands. Additionally, the study found that EDP and MDP were significantly taken up by IGROV-1 ovarian cancer cells compared to IDP-conjugated CdSe/ZnS QDs [ 22 ]. The difference in the cellular uptake of QDs with different target ligands showed that certain ligands are more suitable than others for biological applications.…”

“…QDs can also be conjugated with different types of ligands, which often dictate QDs’ interaction with their surrounding environment [ 17 , 18 , 19 , 20 , 21 ]. The addition of a protective shell and surface ligands increases the solubility and strengthens the structure of QDs [ 9 , 11 , 15 , 22 , 23 , 24 ]. The protective shell also greatly reduces the exposure of the heavy metal contents residing in the core of QDs [ 25 , 26 ], considered to be one of the main mechanisms of QDs’ toxicity.…”

Coordination of Quantum Dots in a Polar Solvent by Small-Molecule Imidazole Ligands

“…For bioimaging applications of quantum dots, − exchange of native hydrophobic ligands with small molecules can achieve water solubility while preserving a small hydrodynamic radius. − Several types of hydrophilic ligands have been identified for ligand exchange of fluorescent QDs. − Numerous studies on thiol anchoring groups show their high binding strength to the QD surface. However, thiols are not an ideal solution for bioimaging applications.…”

Modification of fluorescent nanocrystals with 6-thioguanine: monitoring of drug delivery

“…It should be noted that the surface of QDs can be modified with different types of ligands. The choice of appropriate ligand is a crucial parameter because the ligands affect stability, dispersibility and water solubility of QDs (Abdul Ghani et al 2014). Despite the impact on the physical and chemical parameters, ligands can also influence QDs interaction with cells or living organisms (Biju et al 2010;Jin and Hildebrandt 2012;Karabanovas et al 2014).…”