Nanotech 2010 Vol. 3
Nanotech 2010 Vol. 3
Nanotechnology 2010: Bio Sensors, Instruments, Medical, Environment and Energy

Cancer Nanotechnology Chapter 6

Targeting tumor associated macrophages using clodronate-loaded PLGA nanoparticles

Authors: G. Sharma, P. Karmali, M. Ramirez, Hui Xie, E. Ruoslahti, J. Smith

Affilation: Burnham Institute for Medical Research, United States

Pages: 382 - 385

Keywords: tumor associated macrophages, clodronatge, PLGA nanoparticles, LyP-1 peptide

There is increasing evidence now that tumor associated macrophages (TAMs) play a key role in tumor growth and metastasis by promoting tumor angiogenesis. Macrophages are also prominent in tumor tissues, comprising up to 80% of the cell mass in breast carcinoma. Although therapeutic targeting of TAMs is still in its infancy, the above reasons highlight the importance of TAMs as a validated therapeutic target for nanoparticle-mediated cancer therapy. We propose a novel therapy for cancer by targeting TAMs using clodronate-loaded LyP-1-functionalized PLGA nanoparticles. Clodronate is a promising drug for TAM-mediated tumor therapy. Once delivered inside the cell cytoplasm, it reacts with nonhydrolyzable analogue of ATP resulting in apoptosis. Towards this end we first developed amine-modified, PEGylated PLGA nanoparticles (NPs) encapsulating clodronate as an anti-macrophage drug and showed that it can selectively deplete macrophages while showing little or no toxicity to non-phagocytic cells. We then functionalized these particles with a tumor targeting element and showed that they preferentially accumulate in tumors. Tumor therapy experiments are currently underway to investigate the effect of these NPs on TAM abrogation and tumor suppression.

ISBN: 978-1-4398-3415-2
Pages: 880
Hardcopy: $189.95