Disassembly-Driven Turn-On Fluorescent Nanoprobes for Selective Protein Detection

Abstract

"Switchable" fluorescent probes, which induce changes in the fluorescence properties (e.g., intensity and/or wavelength) only at the intended target protein, are particularly useful for selective protein detection or imaging. However, the strategy for designing such smart probes remains very limited. We report herein a novel mechanism for generating protein-specific "turn-on" fluorescent probes. Our approach uses an amphiphilic, self-assembling compound consisting of a fluorophore and a protein ligand. In the absence of target protein, the probe forms self-assembled aggregates in aqueous solution and displays almost no fluorescence because of efficient quenching. On the other hand, it emits bright fluorescence in response to the target protein through recognition-induced disassembly of the probe. On the basis of this strategy, we successfully developed three types of fluorescent probes that allow the detection of carbonic anhydrase, avidin, and trypsin via turn-on emission signals. It is anticipated that the present supramolecular approach may facilitate the development of new protein-specific switchable fluorescent probes that are useful for a wide range of applications, such as diagnosis and molecular imaging.

New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

“…Mice were intravenously injected with pSNM 1 (10,20,30,40,50,60, and 70 mg/kg) three times on days 0, 3, and 6. Saline and free cabazitaxel in its clinical formulation (10,20,30,40, and 50 mg/kg) were injected as controls. The body weights of the mice were monitored and recorded every 3 days.…”

“…After the tumor reached approximately 50 mm 3 in volume at day 14 after implantation, the animals were randomized into five groups (n ¼ 7 in each group). The mice were intravenously injected with cabazitaxel prodrug-assembled pSNMs (10,20, and 40 mg/kg) a total of three times on days 0, 3, and 6. Saline and cabazitaxel (formulated in polysorbate 80/ethanol, 1:1 v/v, 10 mg/kg) were intravenously injected as controls.…”

“…Healthy ICR mice (n ¼ 10, five females and five males in each group) were intravenously injected with 10,20,30,40,50,60, and 70 mg/kg (cabazitaxel equivalent dose) of pSNM 1 three successive times every 3 days. As comparisons, saline and free cabazitaxel administered in its conventional form were injected.…”

“…Supramolecular chemistry enables noncovalent assembly of individual molecular building blocks (e.g., small-molecule prodrug entities, sensing molecules), thus providing innovative approaches to the creation of fascinating nanostructures for biomedical application (7)(8)(9)(10)(11)(12)(13)(14). For example, Hamachi and colleagues developed a novel sensing mechanism for selective protein detection based on the self-assembly of small amphiphilic probes (9,10,15).…”

“…For example, Hamachi and colleagues developed a novel sensing mechanism for selective protein detection based on the self-assembly of small amphiphilic probes (9,10,15). In their system, the signal is turned off due to self-assembled nanoaggregation of probes but can be turned on in response to molecular disassembly induced by protein recognition.…”