Functionalization of quantum dots with multidentate zwitterionic ligands: impact on cellular interactions and cytotoxicity

Abstract

Surface functionalization of nanoparticles is an important determinant of their interactions with biological compartments at the nano-bio interface. In this paper, a series of multidentate zwitterionic polymeric ligands were synthesized and used to functionalize the surface of quantum dots (QDs). The structure of polymer ligands was designed by changing the molar ratio of reactants and precursors used in the reaction. A three-component micro-emulsion method was developed to improve the efficiency of ligand exchange and avoid cross-linking reactions. Highly stable, compact and biocompatible zwitterionic QDs with different surface charge densities were obtained after ligand exchange. Variation of the surface charge density of QDs was verified by zeta potential measurements. The interaction of zwitterionic QDs with different cancer and normal cell lines (KB 3-1, COLO 205 and HEK 293) was surface charge density dependent. From cell viability studies, it was shown that higher surface charge density resulted in lower cytotoxicity of zwitterionic QDs when incubated with both cancer and normal cell lines. Furthermore, the feasibility of conjugating functionalized QDs (coated with amine zwitterionic polymer ligands) with a biomolecule was demonstrated. This was exemplified by the conjugation of amine zwitterionic QDs with a cRGD peptide, which showed improved interaction of cRGD-QDs with a n b 3 integrin receptors expressed on U87MG glioblastoma tumor cells. Engineering the surface charge density and functionalization of nanoparticles, by multidentate zwitterionic ligands, provides a strategy to tune the surface properties of QDs, which impacts their cytotoxicity and cellular interaction at the nano-bio interface.

Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

“…As most ligands are charged molecules, the NP surface charge is determined by the combinations of ligand densities, materials, and NP formulation strategies. Although recent work was recently carried to address how charge density affects interactions of actively targeted NPs with cells [220] and how optimization of the ligand densities and NP charge can affect cellular uptake [221], it remains unclear what parameters offer the best tumor targeting in vivo .…”

(Bio)conjugation Strategies Applied to Fluorescent Semiconductor Quantum Dots

“…Another issue for this strategy is the presence of amino groups in biological systems, which could lead to an undesired link between the nanoparticle and its target. 43 Aminated QDs have been conjugated, using these homobifunctional coupling agents, to peptides and proteins, 72,73 lectins, 74 antibodies, [75][76][77] receptor ligands 78 and nucleic acids. 79 Ruan et al 73 employed CdSe/ZnS QDs as fluorescentlabeling probes to target the phosphatidylserine exposed in the plasma membrane, due to drug-induced apoptosis.…”

Nanoparticle–blood interactions: the implications on solid tumour targeting

“…6 (2) Nanoparticle surfaces are not coated with a high enough density or long-enough anti-fouling polymer (a threshold unique for each nanoparticle type), which encourages blood protein adsorption, which induces nanoparticles to be taken up by macrophages. 69,70 Nanoparticles functionalized with antibodies, peptide sequences, oligonucleotides, 71 and polyelectrolytes can trigger protein-signaling cascades, induce cell uptake through receptor-mediated endocytosis, [72][73][74] and target subcellular organelles and molecules 75 (Fig. 21 4.2a Serum proteins block nanoparticle active targeting.…”