title: Tuning Cellular Uptake of Molecular Probes by Rational Design of Their Assembly into Supramolecular Nanoprobes.
abstract: 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 protease sensors. In other cases such as extracellular sensing, cellular uptake should be effectively inhibited. Self-assembly of molecular probes into supramolecular nanoprobes presents a potential strategy to alter their interaction mechanisms with cells to promote or reduce their cellular uptake. Here, we report on the design, synthesis, and assembly of peptide-based molecular beacons into supramolecular protease sensors of either spherical or filamentous shapes. We found that positively charged spherical nanobeacons demonstrate much higher cellular uptake efficiency than its monomeric form, thus making them most suitable for intracellular sensing of the lysosomal protease cathepsin B. Our results also suggest that assembly into filamentous nanobeacons significantly reduces their internalization by cancer cells, an important property that can be utilized for probing extracellular protease activities. These studies provide important guiding principles for rational design of supramolecular nanoprobes with tunable cellular uptake characteristics.
authors.affiliation: Department of Chemical and Biomolecular Engineering, and Institute for NanoBioTechnology, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Lye Lin
authors.initials: LL
authors.lastname: Lock
authors.affiliation: Department of Chemical and Biomolecular Engineering, and Institute for NanoBioTechnology, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Reyes
authors.affiliation: Department of Chemical and Biomolecular Engineering, and Institute for NanoBioTechnology, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Biomolecular Engineering, and Institute for NanoBioTechnology, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.|Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore, Maryland 21205, United States.|Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine , 400 North Broadway, Baltimore, Maryland 21231, United States.
authors.forename: Honggang
authors.initials: H
authors.lastname: Cui
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D002401:Cathepsin B / Q000032:analysis* / Q000737:chemistry; D045744:Cell Line, Tumor; D015195:Drug Design; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000201:enzymology
chemical_list: D005456:Fluorescent Dyes; D009842:Oligopeptides; D002401:Cathepsin B