Bioconjugated pluronic triblock-copolymer micelle-encapsulated quantum dots for targeted imaging of cancer: in vitro and in vivo studies

Abstract

Early in this study, CdTe/ZnS core/shell quantum dots (QDs) were encapsulated in carboxylated Pluronic F127 triblock polymeric micelle, to preserve the optical and colloidal stability of QDs in biological fluids. Folic acid (FA) was then conjugated to the surface of QDs for the targeted delivery of the QD formulation to the tumor site, by exploiting the overexpressed FA receptors (FARs) on the tumor cells. Cytotoxicity study demonstrated that the QD formulation has negligible in vitro toxicity. The in vitro study showed that the bioconjugated micelle-encapsulated QDs, but not the unconjugated QDs, were able to efficiently label Panc-1 cancer cells. In vivo imaging study showed that bioconjugated QDs were able to target tumor site after intravenous injection of the formulation in tumor-bearing mice.

Keywords: Bioconjugation; Bioimaging; Pluronics and Nanotoxicity.; Quantum dots; Targeted delivery.

Figure 1

The illustration of synthetic route of carboxylated triblock copolymer F127 (F127COOH).

Figure 2

The illustration of conjugation of FA to the micelle-encapsulated QDs.

Figure 3

UV-vis absorption (black) and PL (red) spectra of monodispersed Pluronic micelle-encapsulated QDs solution.

Figure 4

TEM images CdTe/ZnS QDs dispersed in organic media (a) and aqueous media (b). The scale bars are 5 nm and 50 nm, respectively for a) and b).

Figure 5

DLS plots of micelle-encapsulated QDs before (a) and after (b) conjugating with FA.

Figure 6

Relative cell viability of Panc-1 cells treated with bioconjugated QD formulation for 24 and 48 h post-treatment.

Figure 7

Confocal microscopic images of Panc-1 cells treated with (a) unconjugated micelle-encapsulated QDs (b) FA conjugated micelle-encapsulated QDs and (c) FA conjugated micelle-encapsulated QDs with pre-saturation. In both cases, red represents emission from CdTe/ZnS QDs.

Figure 8

In vivo luminescence imaging of Panc-1 tumor-bearing mice injected with non-bioconjugated QDs (a) and ~4 mg of FA conjugated QDs (b), respectively. All images were acquired under the same experimental conditions. The autofluorescence from mice is coded green and the unmixed QD signal is coded red.

Figure 9

Luminescent image of resected organs from Panc-1 tumor-bearing mouse injected with FA-conjugated micelle-encapsulated QDs. The luminescent image shows the overlays of florescence and transmission images.

Figure 10

H&E-stained tissue sections from mice administered with micelle-encapsulated QDs two weeks post injection. Tissues were harvested from heart (a), kidney (b), liver (c), and spleen (d).