posted on 2016-08-10, 00:00authored byBranislava Janic, Mohammed
PI. Bhuiyan, James R. Ewing, Meser M. Ali
A hallmark
of the tumor microenvironment in malignant tumor is
extracellular acidosis, which can be exploited for targeted delivery
of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle
(NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent
and pHLIP (pH Low Insertion Peptide) into the surface of a G5–PAMAM
dendrimer. pHLIP showed pH-selective insertion and folding into cell
membranes, but only in acidic conditions. We demonstrated that pHLIP-conjugated
Gd44-G5 paramagnetic nanoparticle binds and fuses with
cellular membrane at low pH, but not at normal physiological pH, and
that it promotes cellular uptake. Intracellular trafficking of NPs
showed endosomal/lysosomal path ways.