Highlighting Cancer Cells with Halochromic Switches

Sicheng Tang, Yang Zhang, Ek Raj Thapaliya, Adrienne S. Brown, James N Wilson, Francisco Raymo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Halochromic coumarin-oxazine prefluorophores and targeting folate ligands can be connected covalently to the side chains of amphiphilic polymers. The resulting macromolecular constructs assemble into nanoparticles in aqueous environments. The prefluorophores do not produce any detectable fluorescence at neutral pH, but are converted into fluorophores with intense visible emission at acidic pH. Protonation opens the oxazine heterocycle to shift bathochromically the coumarin absorption and activate fluorescence with a brightness per nanoparticle approaching 5 × 105 M-1 cm-1. This value translates into a 170-fold enhancement relative to the isolated fluorophores dissolved in organic solvent. The folate ligands direct these multicomponent constructs into acidic intracellular compartments of folate-positive cells, where the prefluorophores switch to the corresponding fluorophores and produce fluorescence. The pH-induced activation of the signaling units ensures negligible background fluorescence from the extracellular matrix, which instead limits considerably the contrast accessible with model systems incorporating conventional nonactivatable fluorophores. Furthermore, no intracellular fluorescence can be detected when the very same measurements are performed with folate-negative cells. Nonetheless, control experiments demonstrate that the covalent connection of the prefluorophores to the polymer backbone of the amphiphilic constructs is essential to ensure selectivity. Model systems with prefluorophores noncovalently encapsulated cannot discriminate folate-positive from -negative cells. Thus, our structural design for the covalent integration of activatable signaling units and targeting ligands within the same nanostructured assembly together with the photophysical properties engineered into the emissive components offer the opportunity to highlight cancer cells selectively with high brightness and optimal contrast.

Original languageEnglish (US)
Pages (from-to)92-101
Number of pages10
JournalACS Sensors
Volume2
Issue number1
DOIs
StatePublished - Jan 27 2017

Fingerprint

Folic Acid
Fluorophores
switches
cancer
Fluorescence
Cells
Switches
fluorescence
Oxazines
Ligands
ligands
Luminance
Polymers
brightness
Nanoparticles
nanoparticles
structural design
Protonation
polymers
compartments

Keywords

  • activatable fluorophores
  • amphiphilic polymers
  • cancer detection
  • folate targeting
  • halochromism
  • intracellular pH sensors
  • molecular switches
  • supramolecular nanocarriers

ASJC Scopus subject areas

  • Bioengineering
  • Fluid Flow and Transfer Processes
  • Process Chemistry and Technology
  • Instrumentation

Cite this

Highlighting Cancer Cells with Halochromic Switches. / Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Brown, Adrienne S.; Wilson, James N; Raymo, Francisco.

In: ACS Sensors, Vol. 2, No. 1, 27.01.2017, p. 92-101.

Research output: Contribution to journalArticle

Tang, Sicheng ; Zhang, Yang ; Thapaliya, Ek Raj ; Brown, Adrienne S. ; Wilson, James N ; Raymo, Francisco. / Highlighting Cancer Cells with Halochromic Switches. In: ACS Sensors. 2017 ; Vol. 2, No. 1. pp. 92-101.
@article{86f61cfb8945426b85106d0142a09a29,
title = "Highlighting Cancer Cells with Halochromic Switches",
abstract = "Halochromic coumarin-oxazine prefluorophores and targeting folate ligands can be connected covalently to the side chains of amphiphilic polymers. The resulting macromolecular constructs assemble into nanoparticles in aqueous environments. The prefluorophores do not produce any detectable fluorescence at neutral pH, but are converted into fluorophores with intense visible emission at acidic pH. Protonation opens the oxazine heterocycle to shift bathochromically the coumarin absorption and activate fluorescence with a brightness per nanoparticle approaching 5 × 105 M-1 cm-1. This value translates into a 170-fold enhancement relative to the isolated fluorophores dissolved in organic solvent. The folate ligands direct these multicomponent constructs into acidic intracellular compartments of folate-positive cells, where the prefluorophores switch to the corresponding fluorophores and produce fluorescence. The pH-induced activation of the signaling units ensures negligible background fluorescence from the extracellular matrix, which instead limits considerably the contrast accessible with model systems incorporating conventional nonactivatable fluorophores. Furthermore, no intracellular fluorescence can be detected when the very same measurements are performed with folate-negative cells. Nonetheless, control experiments demonstrate that the covalent connection of the prefluorophores to the polymer backbone of the amphiphilic constructs is essential to ensure selectivity. Model systems with prefluorophores noncovalently encapsulated cannot discriminate folate-positive from -negative cells. Thus, our structural design for the covalent integration of activatable signaling units and targeting ligands within the same nanostructured assembly together with the photophysical properties engineered into the emissive components offer the opportunity to highlight cancer cells selectively with high brightness and optimal contrast.",
keywords = "activatable fluorophores, amphiphilic polymers, cancer detection, folate targeting, halochromism, intracellular pH sensors, molecular switches, supramolecular nanocarriers",
author = "Sicheng Tang and Yang Zhang and Thapaliya, {Ek Raj} and Brown, {Adrienne S.} and Wilson, {James N} and Francisco Raymo",
year = "2017",
month = "1",
day = "27",
doi = "10.1021/acssensors.6b00592",
language = "English (US)",
volume = "2",
pages = "92--101",
journal = "ACS Sensors",
issn = "2379-3694",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Highlighting Cancer Cells with Halochromic Switches

AU - Tang, Sicheng

AU - Zhang, Yang

AU - Thapaliya, Ek Raj

AU - Brown, Adrienne S.

AU - Wilson, James N

AU - Raymo, Francisco

PY - 2017/1/27

Y1 - 2017/1/27

N2 - Halochromic coumarin-oxazine prefluorophores and targeting folate ligands can be connected covalently to the side chains of amphiphilic polymers. The resulting macromolecular constructs assemble into nanoparticles in aqueous environments. The prefluorophores do not produce any detectable fluorescence at neutral pH, but are converted into fluorophores with intense visible emission at acidic pH. Protonation opens the oxazine heterocycle to shift bathochromically the coumarin absorption and activate fluorescence with a brightness per nanoparticle approaching 5 × 105 M-1 cm-1. This value translates into a 170-fold enhancement relative to the isolated fluorophores dissolved in organic solvent. The folate ligands direct these multicomponent constructs into acidic intracellular compartments of folate-positive cells, where the prefluorophores switch to the corresponding fluorophores and produce fluorescence. The pH-induced activation of the signaling units ensures negligible background fluorescence from the extracellular matrix, which instead limits considerably the contrast accessible with model systems incorporating conventional nonactivatable fluorophores. Furthermore, no intracellular fluorescence can be detected when the very same measurements are performed with folate-negative cells. Nonetheless, control experiments demonstrate that the covalent connection of the prefluorophores to the polymer backbone of the amphiphilic constructs is essential to ensure selectivity. Model systems with prefluorophores noncovalently encapsulated cannot discriminate folate-positive from -negative cells. Thus, our structural design for the covalent integration of activatable signaling units and targeting ligands within the same nanostructured assembly together with the photophysical properties engineered into the emissive components offer the opportunity to highlight cancer cells selectively with high brightness and optimal contrast.

AB - Halochromic coumarin-oxazine prefluorophores and targeting folate ligands can be connected covalently to the side chains of amphiphilic polymers. The resulting macromolecular constructs assemble into nanoparticles in aqueous environments. The prefluorophores do not produce any detectable fluorescence at neutral pH, but are converted into fluorophores with intense visible emission at acidic pH. Protonation opens the oxazine heterocycle to shift bathochromically the coumarin absorption and activate fluorescence with a brightness per nanoparticle approaching 5 × 105 M-1 cm-1. This value translates into a 170-fold enhancement relative to the isolated fluorophores dissolved in organic solvent. The folate ligands direct these multicomponent constructs into acidic intracellular compartments of folate-positive cells, where the prefluorophores switch to the corresponding fluorophores and produce fluorescence. The pH-induced activation of the signaling units ensures negligible background fluorescence from the extracellular matrix, which instead limits considerably the contrast accessible with model systems incorporating conventional nonactivatable fluorophores. Furthermore, no intracellular fluorescence can be detected when the very same measurements are performed with folate-negative cells. Nonetheless, control experiments demonstrate that the covalent connection of the prefluorophores to the polymer backbone of the amphiphilic constructs is essential to ensure selectivity. Model systems with prefluorophores noncovalently encapsulated cannot discriminate folate-positive from -negative cells. Thus, our structural design for the covalent integration of activatable signaling units and targeting ligands within the same nanostructured assembly together with the photophysical properties engineered into the emissive components offer the opportunity to highlight cancer cells selectively with high brightness and optimal contrast.

KW - activatable fluorophores

KW - amphiphilic polymers

KW - cancer detection

KW - folate targeting

KW - halochromism

KW - intracellular pH sensors

KW - molecular switches

KW - supramolecular nanocarriers

UR - http://www.scopus.com/inward/record.url?scp=85019603698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019603698&partnerID=8YFLogxK

U2 - 10.1021/acssensors.6b00592

DO - 10.1021/acssensors.6b00592

M3 - Article

C2 - 28722445

AN - SCOPUS:85019603698

VL - 2

SP - 92

EP - 101

JO - ACS Sensors

JF - ACS Sensors

SN - 2379-3694

IS - 1

ER -