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Designing more effective cancer treatments

Author: Arnie Phifer

A potential landmark paper by Notre Dame researchers could help identify and adjust important parameters for designing targeted nanoparticle-based cancer treatments for years to come. At the same time, the results of the study shed light on a decades-long debate among cancer researchers.


The paper, “A Systematic Analysis of Peptide Linker Length and Liposomal Polyethylene Glycol Coating on Cellular Uptake of Peptide-Targeted Liposomes,” is authored by Jared Stefanick, Jonathan Ashley, Tanyel Kiziltepe, and Basar Bilgicer, and appeared in ACS Nano (DOI: 10.1021/nn305663e).



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Bilgicer and his team set out to tackle the problem of “selective targeting and drug delivery to cancer cells” using liposomal nanoparticle formulations. They aim to identify the solutions for overcoming the toxicity problem of small molecule chemotherapeutic agents. Their research also addresses the ongoing debate on the relative effectiveness of active versus passive targeting in nanoparticle-based drug delivery systems.


Their work focused on polyethylene glycol (PEG) coated liposomal nanoparticles and looked at finding the parameters that would enhance the effectiveness of existing cancer treatments, using targeting agents such as HER2 or VLA-4 antagonistic peptides.


“Taken together, the results demonstrate the importance of using the right design elements, such as the appropriate peptide EG-linker length in coordination with the appropriate liposomal PEG coatings, and optimal ligand density in efficient cellular uptake of liposomal nanoparticles,” says Bilgicer.


He adds, “Although one can argue that the in vitro evaluation of nanoparticulate systems may not have direct relevance in in vivo applications, as we demonstrated here, without cellular testing, it would be impossible to identify the design features for achieving enhanced cellular uptake.”


These findings can be used to improve the successful outcomes of ligand-targeted nanoparticles in current and future cancer treatments, which the National Cancer Institute recognizes as an area of potential for paradigm-changing cancer diagnosis and treatment.

 

Originally published by Arnie Phifer at advanceddiagnostics.nd.edu on March 11, 2013.