Intracellular Protein Delivery for Treating Breast Cancer
Annual rept. 15 May 2012 to 14 May 2013
UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
Pagination or Media Count:
Apoptin-containing nanocapsules have been shown to be efficiently internalized by mammalian cells and induce tumor-specific apoptosis in vitro and in vivo. Identification of targeting moieties can further improve the efficacy of these nanoparticles. Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. We demonstrated a targeting strategy by conjugating nanoparticles with a tumor-penetrating peptide, iRGD. The results showed that iRGD could facilate the binding and cellular uptake of nanoparticles. Colocalization data revealed that iRGD-conjugated nanoparticles entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport. In addition, we were able to demonstrate that the biofunctional chelator AmBaSar could be used in the 64Cu labeling of nanoparticles and the positron emission tomography-based images of particle distribution could be obtained at several time points after intravenous administration of nanoparticles. Our data support the further experiment to use iRGD for targeting nanocapsules and to use PET imaging for investigating bioditribution of nanocapsule in vivo.
- Medicine and Medical Research