Highlighting cancer cells with macromolecular probes

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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Conventional fluorophore-ligand constructs for the detection of cancer cells generally produce relatively weak signals with modest contrast. The inherently low brightness accessible per biding event with the pairing of a single organic fluorophore to a single ligand as well as the contribution of unbound probes to background fluorescence are mainly responsible for these limitations. Our laboratories identified a viable structural design to improve both brightness and contrast. It is based on the integration of activatable fluorophores and targeting ligands within the same macromolecular construct. The chromophoric components are engineered to emit bright fluorescence exclusively in acidic environments. The targeting agents are designed to bind complementary receptors overexpressed on the surface of cancer cells and allow internalization of the macromolecules into acidic organelles. As a result of these properties, our macromolecular probes switch their intense emission on exclusively in the intracellular space of target cells with minimal background fluorescence from the extracellular matrix. In fact, these operating principles translate into a 170-fold enhancement in brightness, relative to equivalent but isolated chromophoric components, and a 3-fold increase in contrast, relative to model but non-activatable fluorophores. Thus, our macromolecular probes might ultimately evolve into valuable analytical tools to highlight cancer cells with optimal signal-to-noise ratios in a diversity of biomedical applications.

Original languageEnglish (US)
Title of host publicationColloidal Nanoparticles for Biomedical Applications XII
PublisherSPIE
Volume10078
ISBN (Electronic)9781510605978
DOIs
StatePublished - 2017
EventColloidal Nanoparticles for Biomedical Applications XII 2017 - San Francisco, United States
Duration: Jan 28 2017Jan 31 2017

Other

OtherColloidal Nanoparticles for Biomedical Applications XII 2017
CountryUnited States
CitySan Francisco
Period1/28/171/31/17

Fingerprint

Fluorophores
brightness
cancer
Cells
Luminance
fluorescence
ligands
probes
Fluorescence
Ligands
Neoplasms
structural design
organelles
Intracellular Space
macromolecules
Signal-To-Noise Ratio
signal to noise ratios
Macromolecules
Structural design
Organelles

Keywords

  • Amphiphilic polymers
  • cancer detection
  • fluorescence imaging
  • halochromism
  • molecular switches
  • nanoparticles
  • self-assembly

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Radiology Nuclear Medicine and imaging

Cite this

Tang, S., Zhang, Y., Thapaliya, E. R., Brown, A. S., Wilson, J. N., & Raymo, F. (2017). Highlighting cancer cells with macromolecular probes. In Colloidal Nanoparticles for Biomedical Applications XII (Vol. 10078). [1007814] SPIE. https://doi.org/10.1117/12.2261495

Highlighting cancer cells with macromolecular probes. / Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Brown, Adrienne S.; Wilson, James N; Raymo, Francisco.

Colloidal Nanoparticles for Biomedical Applications XII. Vol. 10078 SPIE, 2017. 1007814.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Tang, S, Zhang, Y, Thapaliya, ER, Brown, AS, Wilson, JN & Raymo, F 2017, Highlighting cancer cells with macromolecular probes. in Colloidal Nanoparticles for Biomedical Applications XII. vol. 10078, 1007814, SPIE, Colloidal Nanoparticles for Biomedical Applications XII 2017, San Francisco, United States, 1/28/17. https://doi.org/10.1117/12.2261495
Tang S, Zhang Y, Thapaliya ER, Brown AS, Wilson JN, Raymo F. Highlighting cancer cells with macromolecular probes. In Colloidal Nanoparticles for Biomedical Applications XII. Vol. 10078. SPIE. 2017. 1007814 https://doi.org/10.1117/12.2261495
Tang, Sicheng ; Zhang, Yang ; Thapaliya, Ek Raj ; Brown, Adrienne S. ; Wilson, James N ; Raymo, Francisco. / Highlighting cancer cells with macromolecular probes. Colloidal Nanoparticles for Biomedical Applications XII. Vol. 10078 SPIE, 2017.
@inproceedings{185b4139a8b64973bbdada75a2a73738,
title = "Highlighting cancer cells with macromolecular probes",
abstract = "Conventional fluorophore-ligand constructs for the detection of cancer cells generally produce relatively weak signals with modest contrast. The inherently low brightness accessible per biding event with the pairing of a single organic fluorophore to a single ligand as well as the contribution of unbound probes to background fluorescence are mainly responsible for these limitations. Our laboratories identified a viable structural design to improve both brightness and contrast. It is based on the integration of activatable fluorophores and targeting ligands within the same macromolecular construct. The chromophoric components are engineered to emit bright fluorescence exclusively in acidic environments. The targeting agents are designed to bind complementary receptors overexpressed on the surface of cancer cells and allow internalization of the macromolecules into acidic organelles. As a result of these properties, our macromolecular probes switch their intense emission on exclusively in the intracellular space of target cells with minimal background fluorescence from the extracellular matrix. In fact, these operating principles translate into a 170-fold enhancement in brightness, relative to equivalent but isolated chromophoric components, and a 3-fold increase in contrast, relative to model but non-activatable fluorophores. Thus, our macromolecular probes might ultimately evolve into valuable analytical tools to highlight cancer cells with optimal signal-to-noise ratios in a diversity of biomedical applications.",
keywords = "Amphiphilic polymers, cancer detection, fluorescence imaging, halochromism, molecular switches, nanoparticles, self-assembly",
author = "Sicheng Tang and Yang Zhang and Thapaliya, {Ek Raj} and Brown, {Adrienne S.} and Wilson, {James N} and Francisco Raymo",
year = "2017",
doi = "10.1117/12.2261495",
language = "English (US)",
volume = "10078",
booktitle = "Colloidal Nanoparticles for Biomedical Applications XII",
publisher = "SPIE",

}

TY - GEN

T1 - Highlighting cancer cells with macromolecular probes

AU - Tang, Sicheng

AU - Zhang, Yang

AU - Thapaliya, Ek Raj

AU - Brown, Adrienne S.

AU - Wilson, James N

AU - Raymo, Francisco

PY - 2017

Y1 - 2017

N2 - Conventional fluorophore-ligand constructs for the detection of cancer cells generally produce relatively weak signals with modest contrast. The inherently low brightness accessible per biding event with the pairing of a single organic fluorophore to a single ligand as well as the contribution of unbound probes to background fluorescence are mainly responsible for these limitations. Our laboratories identified a viable structural design to improve both brightness and contrast. It is based on the integration of activatable fluorophores and targeting ligands within the same macromolecular construct. The chromophoric components are engineered to emit bright fluorescence exclusively in acidic environments. The targeting agents are designed to bind complementary receptors overexpressed on the surface of cancer cells and allow internalization of the macromolecules into acidic organelles. As a result of these properties, our macromolecular probes switch their intense emission on exclusively in the intracellular space of target cells with minimal background fluorescence from the extracellular matrix. In fact, these operating principles translate into a 170-fold enhancement in brightness, relative to equivalent but isolated chromophoric components, and a 3-fold increase in contrast, relative to model but non-activatable fluorophores. Thus, our macromolecular probes might ultimately evolve into valuable analytical tools to highlight cancer cells with optimal signal-to-noise ratios in a diversity of biomedical applications.

AB - Conventional fluorophore-ligand constructs for the detection of cancer cells generally produce relatively weak signals with modest contrast. The inherently low brightness accessible per biding event with the pairing of a single organic fluorophore to a single ligand as well as the contribution of unbound probes to background fluorescence are mainly responsible for these limitations. Our laboratories identified a viable structural design to improve both brightness and contrast. It is based on the integration of activatable fluorophores and targeting ligands within the same macromolecular construct. The chromophoric components are engineered to emit bright fluorescence exclusively in acidic environments. The targeting agents are designed to bind complementary receptors overexpressed on the surface of cancer cells and allow internalization of the macromolecules into acidic organelles. As a result of these properties, our macromolecular probes switch their intense emission on exclusively in the intracellular space of target cells with minimal background fluorescence from the extracellular matrix. In fact, these operating principles translate into a 170-fold enhancement in brightness, relative to equivalent but isolated chromophoric components, and a 3-fold increase in contrast, relative to model but non-activatable fluorophores. Thus, our macromolecular probes might ultimately evolve into valuable analytical tools to highlight cancer cells with optimal signal-to-noise ratios in a diversity of biomedical applications.

KW - Amphiphilic polymers

KW - cancer detection

KW - fluorescence imaging

KW - halochromism

KW - molecular switches

KW - nanoparticles

KW - self-assembly

UR - http://www.scopus.com/inward/record.url?scp=85020196237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020196237&partnerID=8YFLogxK

U2 - 10.1117/12.2261495

DO - 10.1117/12.2261495

M3 - Conference contribution

VL - 10078

BT - Colloidal Nanoparticles for Biomedical Applications XII

PB - SPIE

ER -