Intracellular Delivery: A Multifunctional and Modular Approach - Intracellular Delivery: Fundamentals and Applications - page 207

Fig. 4 Intracellular trafficking of rhodamine-PE- labeled and FITC-dextran-loaded TATp-
liposomes within BT20 cells. Typical patterns of intracellular localization and integrity of
TATp-liposome after 1 h. ( a ), DIC light; ( b ), DIC with an rhodamine filter; ( c ), DIC with an
FITC filter; ( d ), DIC composite of ( b )-( c ). (Magnification, ×400) (Modified from Torchilin
2005a )
nanocarriers may serve as good solution to this problem for delivery of anticancer
drugs at least in certain cases. We prepared and studied paclitaxel-loaded TATp
containing PEG-PE micelles (Sawant and Torchilin 2009 ). Such paclitaxel-loaded
micelles were prepared using PEG 750 -PE as the main micelle-forming component
with the addition of 2.5 mol% TATp-PEG 1000 -PE to promote direct unhindered
contact with cells.
The in vitro cell interaction of the TATp-bearing PEG-PE micelles was confirmed
by fluorescence microscopy with 4T1 cells (Fig. 5 ). Plain micelles composed of
PEG 750 -PE demonstrated limited interaction with the cells (Fig. 5a ). However, the
use of the TATp-bearing PEG 750 -PE micelles resulted in a strong interaction with
the cells (Fig. 5b ). This enhanced interaction also resulted in increased in vitro
cytotoxicity against MCF-7 and 4T1 cells with paclitaxel-loaded TATp-bearing
micelles compared to paclitaxel-loaded micelles without TATp at both 5 and 50 nM
paclitaxel concentrations.
For in vivo studies, to avoid any unwanted distribution of paclitaxel-loaded
TATp-micelles, micelles were injected intratumorally in mice and tumors were
harvested after 48 h. Nuclear DNA fragmentation in tumor sections undergoing