In vitro evaluation of theranostic polymeric micelles for imaging and drug delivery in cancer

Abstract

For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs) and anti-cancer drug, doxorubicin (Dox), were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of <50 nm for the micellar formulations with very narrow size distribution. A sustained release of the drug was observed from the co-encapsulated micellar formulation. In vitro optical fluorescence imaging and cytotoxicity studies with HeLa cell line demonstrated the potential of these micellar systems as efficient optical imaging and therapeutic probes.

Keywords: Cancer; Drug Delivery; Imaging; Theranostic Polymeric Micelles.

Figure S1

(Scheme 1) Schematic representation of the synthetic strategy of the phospholipid based micelles encapsulating CdSe QDs and doxorubicin.

Figure 1

Size distribution and morphology studies of the micellar formulations by Dynamic light scattering measurements (left panel) and Transmission electron Microscopy (right panel). TEM image of (A) QD-Dox micelles, (B) QDs dispersed in toluene and (C) blank micelles. Inset shows the magnified image of the QD-Dox micelles.

Figure 2

UV-Visible absorbance spectra of CdSe QDs and doxorubicin in free form in chloroform as well as in encapsulated form in micelles.

Figure 3

Photoluminescence spectra of the CdSe QDs and doxorubicin in free form in chloroform as well as in encapsulated form in micelles. The spectrum of QDs in QD-Dox micelles is enlarged on the left for clarity. (See supporting info for non-normalized data).

Figure 4

Release kinetics study for estimating the release of the doxorubicin from the QD-Dox micelles.

Figure 5

Confocal images of the HeLa cells incubated with QD micelles for 2 hrs (upper panel) and 24 hrs (lower panel). Same instrument settings were used to acquire all the images.

Figure 6

Confocal images of the HeLa cells incubated with QD-Dox micelles for 2 hrs. The upper panel shows the images acquired from the three different channels and the lower panel shows the overlaid images.

Figure 7

Cytotoxicity assay (MTS assay) carried out with different micellar formulations of QD micelles, QD-Dox micelles and free Dox in HeLa cell line. All the formulations were incubated for 24 hrs.