August 7, 2006
Smart Multifunctional Nanoparticle for Drug Delivery
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, 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.
This work is detailed in a paper titled, “‘SMART’ drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers.” This paper was published online in advance of print publication. An abstract is available at the journal’s website.