title: pH-Dependent Cellular Internalization of Paramagnetic Nanoparticle.
abstract: 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.
authors.affiliation: Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Branislava
authors.initials: B
authors.lastname: Janic
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Mohammed Pi
authors.initials: MP
authors.lastname: Bhuiyan
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Ewing
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Meser M
authors.initials: MM
authors.lastname: Ali
keywords: Cell internalization; MRI; intracellular trafficking; pH sensing probe; paramagnetic nanoparticle