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Increasing the affinity of cationized polyacrylamide-paclitaxel nanoparticles towards colon cancer cells by a surface
Sanjay Tiwari1, Boaz Tirosh1, Abraham Rubinstein1
1The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem, 91120, Israel.
Abstract:
Nanoparticles of cationized polyacrylamide (CPAA NP), decorated with the recognition peptide VRPMPLQ (to produce CPAA-Pep NP), were prepared, characterized and tested biologically. They were designed to target dysplasia regions in the colon, characterized by overexpressed sialic acid. This targetability was augmented by the addition of VRPMPLQ. Their mean hydrodynamic size was 137nm with narrow size distribution and positive zeta potential. When incubated with three types of colon cancer cells, a 10-fold increase in the cell's uptake was found for the CPAA-Pep NP compared with the CPAA NP. The use of a scrambled sequence of the VRPMPLQ peptide and competition studies, employing excess of the free peptide verified the specific nature of the NP cellular uptake. Nanoparticles loaded with paclitaxel with and without VRPMPLQ indicated an improved pro-apoptotic activity of the CPAA-Pep NP. It is speculated that both positive charge and the presence of VRPMPLQ could serve as an improved strategy to deliver nanoparticles loaded with cytotoxic drugs for the treatment of colon cancer.
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