Multiparameter Single-Molecular Studies of Novel Cancer Inhibitors and Drug Delivery Systems

We hypothesized that membrane localization of a major transcription protein (STAT3) will have profound therapeutic benefits by inhibiting its nuclear localization and therefore its well-recognized aberrant function as a master regulator of events leading to the cancer phenotype. Fluorescence imaging and single-molecule spectroscopy addressed the binding potency of new STAT3 recognition sequences and their efficacy for sequestering the STAT3 protein to the lipid membrane in liposome model systems. These in-vitro results were confirmed by live cell imaging and biochemical data on tumor cells. This novel inhibitor modality for targeting the aberrant motility of cytosolic signaling proteins in human disease could have significant therapeutic value.

We designed Lipogels consisting of a micron-sized polymeric (pNIPAM) sphere coated by a lipid shell. Using a combination of fluorescence and NMR spectroscopy techniques, we demonstrated that the external lipid layer is unilamellar, continuous  and impermeable, and that the Lipogels retain the essential thermo-responsive behavior of the pNIPAM polymer, with a volume-phase transition near 32 °C. These properties of Lipogels can prove useful in drug delivery applications and in fundamental biophysical studies of membranes.

 

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