(657f) Design and Construction of Supramolecular Imaging Agents
Intracellular sensing of pathologically relevant biomolecules could provide essential information for accurate evaluation of disease staging and progression, yet the poor cellular uptake of water soluble molecular probes limits their use as effective protease sensors. Rational design of molecular probes capable of self-assembling into supramolecular nanoprobes presents a potential strategy to alter their interaction mechanisms with cells thus promoting their effective cellular entry and intracellular accumulation. Herein we report on the design and synthesis of peptide-based self-assembling molecular beacons that could spontaneously associate into supramolecular protease sensors of either spherical or cylindrical shapes depending upon both their growth kinetics and assembly conditions. Our confocal imaging and flow cytometry results reveal that cancer cells experience difficulties internalizing high-aspect-ratio cylindrical nanobeacons regardless of their charge status, but could rapidly internalize positively charged spherical nanobeacons. These studies corroborate the shape-dependent cellular uptake of filamentous nanostructures and the charge-dependent internalization of spherical nanoparticles, and more importantly provide guiding principles for rational design of supramolecular nanoprobes with tunable cellular uptake characteristics.