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Posted: August 7, 2007
Smart multifunctional nanoparticle for drug delivery
(Nanowerk News) Attaching two different targeting molecules to a nanoscale liposome, a team of investigators at Northeastern University has created a nanoparticle that targets malignant cells and triggers rapid uptake by those cells. In addition, this new long-circulating nanoparticle is designed to be taken up by cells only when exposed to the acidic conditions found inside tumors.
Reporting its work in the journal Bioconjugate Chemistry ("SMART" Drug Delivery Systems: Double-Targeted pH-Responsive Pharmaceutical Nanocarriers), a group headed by Vladimir Torchilin, Ph.D., describes its initial work in creating a "smart" multifunctional nanoscale drug delivery agent. The starting point for this delivery vehicle was a liposome coated with a form of poly(ethylene glycol) (PEG), modified so that it falls apart at low pH. The investigators then added a monoclonal antibody for cell targeting and either the molecule biotin or a peptide known as TAT to trigger rapid cell uptake of the nanoparticles. The researchers attached the monoclonal antibody using a long linking molecule that allows the antibody to stick out above the PEG coating. In contrast, the investigators used a short linker to attach biotin or the TAT peptide, leaving these molecules buried within the PEG layer.
Tests using cells growing in culture showed that these nanoparticles targeted cells containing a surface protein recognized by the monoclonal antibody, but the particles were not taken in by these cells at a normal physiologic pH of 7.4. However, when the researchers lowered the pH of the culture medium to between 5.0 and 6.0, to mimic the acidic conditions within a tumor, the liposomes were readily taken up by the cultured cells. In principle, this double targeting mechanism, which would be responsive to the distinct local environment of a tumor, could provide a means of improving the relative distribution of anticancer agents between tumor and health tissue.