Cytotoxicity of Quantum Dots Used for In Vitro Cellular Labeling: Role of QD Surface Ligand, Delivery Modality, Cell Type, and Direct Comparison to Organic Fluorophores

Abstract

Interest in taking advantage of the unique spectral properties of semiconductor quantum dots (QDs) has driven their widespread use in biological applications such as in vitro cellular labeling/imaging and sensing. Despite their demonstrated utility, concerns over the potential toxic effects of QD core materials on cellular proliferation and homeostasis have persisted, leaving in question the suitability of QDs as alternatives for more traditional fluorescent materials (e.g., organic dyes, fluorescent proteins) for in vitro cellular applications. Surprisingly, direct comparative studies examining the cytotoxic potential of QDs versus these more traditional cellular labeling fluorophores remain limited. Here, using CdSe/ZnS (core/shell) QDs as a prototypical assay material, we present a comprehensive study in which we characterize the influence of QD dose (concentration and incubation time), QD surface capping ligand, and delivery modality (peptide or cationic amphiphile transfection reagent) on cellular viability in three human cell lines representing various morphological lineages (epithelial, endothelial, monocytic). We further compare the effects of QD cellular labeling on cellular proliferation relative to those associated with a panel of traditionally employed organic cell labeling fluorophores that span a broad spectral range. Our results demonstrate the important role played by QD dose, capping ligand structure, and delivery agent in modulating cellular toxicity. Further, the results show that at the concentrations and time regimes required for robust QD-based cellular labeling, the impact of our in-house synthesized QD materials on cellular proliferation is comparable to that of six commercial cell labeling fluorophores. Cumulatively, our results demonstrate that the proper tuning of QD dose, surface ligand, and delivery modality can provide robust in vitro cell labeling reagents that exhibit minimal impact on cellular viability.

Mind your P's and Q's: the coming of age of semiconducting polymer dots and semiconductor quantum dots in biological applications

“…In reality, toxicity is a complex issue with a notable disconnect between studies with cell models and those with animal models: cytotoxicity associated with QDs does not directly translate into toxicity in animal models [10 ,11 ]. Although it is prudent to remain cautious about the prospect of in vivo administration of QDs to humans, the potential toxicity of QDs is not a compelling argument against their use as cellular or in vivo probes for fundamental studies on model systems, but rather a directive to use high-quality and well-characterized materials, which many studies have shown to be non-cytotoxic at doses and exposures relevant to experiments (for recent examples, see [12,13]). Moreover, it is impractical to argue that QDs should be avoided for in vitro assays because of their 'toxic' cadmium content -the amount of QDs in a typical assay ( 10 À11 mol QD per sample, or 100 mg Cd) is no more cadmium than the average North American or European adult consumes as part of their weekly diet ($175 mg) [14].…”

Photoluminescent nanoplatforms in biomedical applications

“…Review papers summarizing the studies performed on the toxicity of different photoluminescent nanoparticles have been reported, including gold nanoparticles [193][194][195][196], QDs [197][198][199][200][201], lanthanide-based nanoparticles [179,[202][203][204], and C-dots [205]. However, individual toxicity evaluations need to be completed for each developed nanoplatform to completely assure its safety for biomedical applications.…”

Carbon Quantum Dots: Synthesis, Characterization and Biomedical Applications

“…They have the ability to elucidate the pharmacokinetics and pharmacodynamics of drug applicant and serve as a "traceable" drug delivery system. [1][2][3][4][5] In 1984, the Russian physicist Ekimov first discovered QDs in glass crystals. After 1984, a systemic advancement in pharmaceutical sciences was driven, and a relationship was established between the size and band gap for semiconductor nano particles (by applying a particle in a sphere model) approximation to the wave function for bulk semiconductors.…”