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Multifunctional liposomes for enhanced tumor targeting.

A. Apte, E. Koren, V.P. Torchilin
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, US

Keywords: Immunoliposomes, 2C5, TAT peptide, pH-sensitive, drug delivery


Delivery of therapeutic agents mediated by nanoparticulate drug delivery systems is developing rapidly, an example of which is liposome based drug delivery. Cell penetrating peptides (CPP), such as trans-activating transcriptional activator (TAT), have produced positive results in vitro and in vivo as drug delivery agents, but undergo rapid degradation in body. However, a protective polymer on the surface of nanoparticulates can prevent CPP’s proteolytic degradation and detach at a tumor’s relatively acidic extracellular pH exposing CPP. Ability of monoclonal antibody 2C5 to target nucleosomes on tumor cell surface is also established. With this in mind, multifunctional liposomes were prepared containing on their surface: CPP -TATp-PEG1000-PE conjugate, long chain pH-sensitive polymer PEG2000-hydrazone-PE, and monoclonal antibody 2C5 linked PEG3400-PE. When pre-incubated at acidic pH, enhanced tumor cell interaction of these liposomes was observed, indicating TATp deshielding compared to neutral pH. mAb 2C5 on the surface further increased the interaction of these liposomes with tumor cells.
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