Sharma G., Karmali P., Ramirez M., Xie Hui, Ruoslahti E., Smith J.
Burnham Institute for Medical Research, US
Keywords: clodronatge, LyP-1 peptide, PLGA nanoparticles, tumor associated macrophages
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.
Journal: TechConnect Briefs
Volume: 3, Nanotechnology 2010: Bio Sensors, Instruments, Medical, Environment and Energy
Published: June 21, 2010
Pages: 382 - 385
Industry sector: Medical & Biotech
Topics: Biomaterials, Cancer Nanotechnology
ISBN: 978-1-4398-3415-2