Imaging pancreatic cancer using bioconjugated InP quantum dots

Abstract

In this paper, we report the successful use of non-cadmium-based quantum dots (QDs) as highly efficient and nontoxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)-zinc sulfide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in nonaqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjugation with pancreatic cancer specific monoclonal antibodies, such as anticlaudin 4 and antiprostate stem cell antigen (anti-PSCA), to the functionalized InP/ZnS QDs, allowed specific in vitro targeting of pancreatic cancer cell lines (both immortalized and low passage ones). The receptor-mediated delivery of the bioconjugates was further confirmed by the observation of poor in vitro targeting in nonpancreatic cancer based cell lines which are negative for the claudin-4-receptor. These observations suggest the immense potential of InP/ZnS QDs as non-cadmium-based safe and efficient optical imaging nanoprobes in diagnostic imaging, particularly for early detection of cancer.

Figure 1

(a) & (b) TEM image of water-dispersible InP/ZnS QDs at different magnification.

Figure 2

XRD profile of InP/ZnS QDs.

Figure 3

(a) Absorption and emission spectra of InP/ZnS QDs dispersed in chloroform. (b) Photoluminescence stability of InP/ZnS QDs under different pH conditions after dispersing the QDs for 48 hours.

Figure 4

(a) DLS plot of InP/ZnS QDs water dispersion. (b) Time-dependent of hydrodynamic diameter of InP/ZnS QDs dispersed in PBS buffer.

Figure 5

Confocal microscopic images of (a) MiaPaCa cells treated with anti-claudin 4-conjugated InP/ZnS QDs; (b) MiaPaCa cells treated with unconjugated InP/ZnS QDs; (c) MiaPaCa cells treated with anti-PSCA-conjugated InP/ZnS QDs; (d) XPA3 cells treated with anti-claudin 4-conjugated InP/ZnS QDs; and (e) KB (human nasopharyngeal epidermal carcinoma cell line) cells treated with anti-claudin 4-conjugated InP/ZnS QDs. In all cases, blue represents emission from Hoechst 33342 and red represents emission from InP/ZnS QDs.

Figure 6

Flow cytometry data showing the relative uptake of unconjugated QDs and PSCA conjugated QDs in MiaPaCa cells. The number of positively labeled cells was represented as the percentage of total cell counts.

Figure 7

In vitro cell viability of MiaPaCa treated with varying concentrations of InP/ZnS QDs for 24 and 48 hours. Percentage cell viability of the treated cells is calculated relative to that of untreated cells (with arbitrarily assigned 100 % viability).

Scheme 1

Schematic illustration showing the formation of the water-dispersible InP/ZnS QD-bioconjugates.