Defect engineered bioactive transition metals dichalcogenides quantum dots

Abstract

Transition metal dichalcogenide (TMD) quantum dots (QDs) are fundamentally interesting because of the stronger quantum size effect with decreased lateral dimensions relative to their larger 2D nanosheet counterparts. However, the preparation of a wide range of TMD QDs is still a continual challenge. Here we demonstrate a bottom-up strategy utilizing TM oxides or chlorides and chalcogen precursors to synthesize a small library of TMD QDs (MoS₂, WS₂, RuS₂, MoTe₂, MoSe₂, WSe₂ and RuSe₂). The reaction reaches equilibrium almost instantaneously (~10-20 s) with mild aqueous and room temperature conditions. Tunable defect engineering can be achieved within the same reactions by deviating the precursors' reaction stoichiometries from their fixed molecular stoichiometries. Using MoS₂ QDs for proof-of-concept biomedical applications, we show that increasing sulfur defects enhanced oxidative stress generation, through the photodynamic effect, in cancer cells. This facile strategy will motivate future design of TMDs nanomaterials utilizing defect engineering for biomedical applications.

Fig. 1

Benign aqueous room temperature bottom-up synthesis of MoS₂ QDs. a Preparation of MoS₂ QDs with bottom-up strategy. b Easy and scalable aqueous MoS₂ colloidal suspension. Synthesis step takes less than 10–20 s (also refer to Supplementary Movie 1). c Ultrasmall but consistent as-synthesized MoS₂ QDs. Inset: Distribution of MoS₂ QDs size measured (ImageJ, n = 200). Scale bar: 100 nm. d HRTEM (Scale bar: 5 nm), e XRD and f UV-vis absorption spectra of MoS₂ QDs showing a distinctively different nanomaterial from exfoliated MoS₂ nanosheets

Fig. 2

Surfactant effect on quality of MoS₂ QDs. a Size of the BSA and MoS₂ QDs determined by DLS. b Schematic illustration of possible BSA interactions with one MoS₂ QD. c TEM images of MoS₂ QDs synthesized with BSA, Cys, Glu and Poly-Arg. Scale bar: 200 nm. d Statistical analysis of the size distributions of MoS₂ QDs synthesized with different biological surfactants. e Binding energy of major functional groups of BSA to MoS₂ QDs

Fig. 3

Illustration of the bottom-up synthesis of TMD QDs under mild condition. a In this study, only the synthesis of commonly reported TMDs (MoS₂, WS₂, RuS₂, MoTe₂, MoSe₂, WSe₂ and RuSe₂) QDs were showed. b Extrapolating the synthesis method to other TMD QDs synthesis may present an universal method to synthesis the various TMDs QDs

Fig. 4

TEM images of other TMDs QDs synthesized under similarly mild conditions. a–f TEM images of WS₂, RuS₂, MoTe₂, MoSe₂, WSe₂ and RuSe₂ QDs. Insets: Stable colloidal suspension appearance of TMDs dispersed in aqueous condition. TMDs QDs have consistent sizes. Scale bar: 100 nm

Fig. 5

Engineering sulfur defects into MoS₂ QDs through stoichiometric reaction control. a Adjusting precursor ratios produces three kinds of MoS₂ suspension in pure water. TEM images show narrow size distribution. Scale bar: 50 nm. b Different stoichiometry does not affect overall size of QD MoS₂. (Distributions derived from at least n = 200). HRTEM images show dislocations and distortions of lattice planes in MoS₂ QDs due to intrinsic defects. Scale bar: 2 nm. c XRD show gradually enlarged lattice constants with decreasing stoichiometry in three MoS₂ QDs. d PL spectrum show different emission intensities of the three MoS₂ QDs at the same optical absorption. e XPS reveal the defect engineering was in the form of MoO_xS_2-x by the substitution of oxygen for sulfur. f Structural model of the reaction pathway of MoS₂ QDs and defect engineering in MoS₂ QDs as a function of precursor stoichiometry

Fig. 6

Positive correlation between sulfur defects and photodynamic efficiency in QDs. a Absorption spectra of three kinds of MoS₂ QDs in the presence of ABDA under light irradiation (0.1 W cm-2, 8 min). b Typical decomposition rate of the photosensitizing process, where A₀ is the absorbance of initial absorbance of ABDA and A is the absorbance of ABDA under light irradiation at different time points (Full data plots can be found as Supplementary Figure 19). c Relative ¹O₂ quantum yield of two MoS₂ QDs groups relative to MoS₂-D_L QDs. Mean ± SD, n = 4, Student’s t-test, p* < 0.05. d Detection of ROS generation at cellular level in colon cancer cell line, SW480 by intracellular ROS indicator H₂DCFH-DA. Scale bar: 50 μm. e Structure illustration for the substitution of oxygen for sulfur within MoS₂ lattices. f Calculated density of states of MoS₂ QDs show the defects reduce the bandgap. g More sulfur defects induce stronger binding affinity of ³O₂ to MoS₂. h Proposed defect related ¹O₂ generation mechanism of MoS₂ QDs

Fig. 7

MoS₂ QDs with more S defects produce more oxidative stress in cancer cells. a MoS₂ QDs treatment (without light) on human endothelial cells (HMVEC) showed negligible cytotoxicity, negligible excessive ROS generation and low apoptosis induction. The measurements were performed in triplicate. b Calcein AM and PI co-staining and c cell viabilities of SW480 cells incubated with different defect laden MoS₂ QDs under white light exposure. The measurements were performed in triplicate. d MoS₂-D_H showed the highest size reduction of 3D tumor spheroids assay. This implied high penetration of QDs into the interior of the 3D tumor spheroids mass with the highest defect group producing the highest oxidative stress that killed the cells. e Quantification of 3D tumor spheroids area post treatment and laser excitation with MoS₂-D_H showing the greatest cell death amongst the three MoS₂ groups. Mean ± SD, n = 10, Student’s t test, p^# < 0.05. Scale bar: 100 μm