Novel Approach to Imaging of Nano-Drug-Delivery Carriers Based on Raman Microscopy

Student: Tatyana Chernenko
Department: Chemistry
Advisor: Max Diem

Abstract

Figure 1: Raman images of cells incubated with different types of drug delivery systems. (A) An MCF-7 cell treated with TATp-modified DSPC-d70 liposomes; (B) a HeLa cell inoculated with a TATp-PEG-PE micelle system; and (C) a HeLa cell exposed to PCL-Pluronic®-bas

Cell targeting has been the growing field of interest in gene therapy and anticancer treatments. Of particular interest are pharmaceutical drug delivery systems, such as micelles and liposomes. In order to monitor their uptake, intracellular fate and determine their sites of action, fluorescence microscopy has been widely used in the biological field as an imaging technique. However, this method provides a number of limitations which include low contrast or photo-bleaching of the sample as well as the need for introduction of extrinsic dyes or stains into the system. Although they have been extensively used, fluorescing labels, introduced intracellularly, may potentially alter the biochemical properties of the molecule of interest.

We thus employ Raman micro-spectroscopic techniques, which are based on vibrational spectroscopy coupled with optical microscopy to provide a non-invasive and non-destructive method for cellular imaging. This technique provides a novel method to spectroscopically map the biochemical components of an individual cell. Spectra can be recorded from different organelles or locations within the cell and spectral differences identified that characterize biochemical components. We propose to utilize this technique to identify the presence of liposomes within a cell and map their concentration and distribution therein. In addition, the sensitivity of liposome detection can be substantially increased by fabricating them entirely from deuterated phospholipids, which provide very strong Raman signals.

Liposomal research is still underway and their sub-cellular targets still under scrutiny. Hence the dire need for the ease of chemical characterization of the liposomes themselves as well as their docking sites is still one of the top priorities. We thus offer a novel approach to monitoring liposomal targeting, which can ultimately be applied to in vivo studies.