Tumor microenvironment-responsive fluorogenic nanoprobe for ratiometric dual-channel imaging of lymph node metastasis

Hong Jun Cho, Seokyung Lee, Sung Jun Park, Yong Deok Lee, Keunsoo Jeong, Jae Hyung Park, Yoon Sik Lee, Bokyung Kim, Han Sin Jeong, Sehoon Kim

Research output: Contribution to journalArticle

Abstract

Fluorogenic nanoprobes capable of providing microenvironmental information have extensively been developed to improve the diagnostic accuracy for early or metastatic cancer detection. In cancer-associated microenvironment, matrix metalloproteinase-2,9 (MMP-2,9) has drawn attention as a representative enzymatic marker for diagnosis, prognosis, and prediction of various cancers, which is overexpressed in the primary site as well as metastatic regions. Here, we devised dual-emissive fluorogenic nanoprobe (DFNP) emitting both MMP-2,9-sensitive and insensitive fluorescence signals, for accurate monitoring of the MMP-2,9 activity in metastatic regions. DFNP was nanoscopically constructed by amphiphilic self-assembly between a constantly fluorescent polymer surfactant labeled with Cy7 (F127-Cy7) and an initially nonfluorescent hydrophobic peptide (Cy5.5-MMP-Q) that is fluorogenic in response to MMP-2,9. Ratiometric readout (Cy5.5/Cy7) by dual-channel imaging could normalize the enzyme-responsive sensing signal relative to the constantly emissive internal reference that reflects the probe amount, allowing for semi-quantitative analysis on the MMP-2,9-related tissue microenvironment. In addition to the dual-channel emission, the nanoconstructed colloidal structure of DFNP enabled efficient accumulation to lymph node in vivo. Because of these two colloidal characteristics, when injected intradermally to a mouse model of lymph node metastasis, DFNP could produce reliable ratiometric signals to provide information on the MMP-2,9 activity in the lymph nodes depending on metastatic progression, which corresponded well to the temporal histologic analysis. Furthermore, ratiometric lymph node imaging with DFNP after photodynamic therapy allowed for monitoring a therapeutic response to the given cancer treatment, demonstrating diagnostic and prognostic potential of the nanoconstructed colloidal sensor of tumor microenvironment in cancer treatment.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalColloids and Surfaces B: Biointerfaces
Volume179
DOIs
Publication statusPublished - 2019 Jul 1

Fingerprint

Nanoprobes
Tumor Microenvironment
lymphatic system
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
metastasis
Tumors
tumors
Lymph Nodes
Neoplasm Metastasis
Imaging techniques
cancer
matrices
UCON 50-HB-5100
Oncology
Neoplasms
Photodynamic therapy
prognosis
Monitoring
Photochemotherapy

Keywords

  • Cancer diagnosis
  • Dual-channel fluorescence imaging
  • Fluorogenic nanoprobe
  • Lymph node metastasis
  • Matrix metalloproteinase-2,9

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

Cite this

Tumor microenvironment-responsive fluorogenic nanoprobe for ratiometric dual-channel imaging of lymph node metastasis. / Cho, Hong Jun; Lee, Seokyung; Park, Sung Jun; Lee, Yong Deok; Jeong, Keunsoo; Park, Jae Hyung; Lee, Yoon Sik; Kim, Bokyung; Jeong, Han Sin; Kim, Sehoon.

In: Colloids and Surfaces B: Biointerfaces, Vol. 179, 01.07.2019, p. 9-16.

Research output: Contribution to journalArticle

Cho, Hong Jun ; Lee, Seokyung ; Park, Sung Jun ; Lee, Yong Deok ; Jeong, Keunsoo ; Park, Jae Hyung ; Lee, Yoon Sik ; Kim, Bokyung ; Jeong, Han Sin ; Kim, Sehoon. / Tumor microenvironment-responsive fluorogenic nanoprobe for ratiometric dual-channel imaging of lymph node metastasis. In: Colloids and Surfaces B: Biointerfaces. 2019 ; Vol. 179. pp. 9-16.
@article{fb0c415019fc46b5b2728483aa2e211e,
title = "Tumor microenvironment-responsive fluorogenic nanoprobe for ratiometric dual-channel imaging of lymph node metastasis",
abstract = "Fluorogenic nanoprobes capable of providing microenvironmental information have extensively been developed to improve the diagnostic accuracy for early or metastatic cancer detection. In cancer-associated microenvironment, matrix metalloproteinase-2,9 (MMP-2,9) has drawn attention as a representative enzymatic marker for diagnosis, prognosis, and prediction of various cancers, which is overexpressed in the primary site as well as metastatic regions. Here, we devised dual-emissive fluorogenic nanoprobe (DFNP) emitting both MMP-2,9-sensitive and insensitive fluorescence signals, for accurate monitoring of the MMP-2,9 activity in metastatic regions. DFNP was nanoscopically constructed by amphiphilic self-assembly between a constantly fluorescent polymer surfactant labeled with Cy7 (F127-Cy7) and an initially nonfluorescent hydrophobic peptide (Cy5.5-MMP-Q) that is fluorogenic in response to MMP-2,9. Ratiometric readout (Cy5.5/Cy7) by dual-channel imaging could normalize the enzyme-responsive sensing signal relative to the constantly emissive internal reference that reflects the probe amount, allowing for semi-quantitative analysis on the MMP-2,9-related tissue microenvironment. In addition to the dual-channel emission, the nanoconstructed colloidal structure of DFNP enabled efficient accumulation to lymph node in vivo. Because of these two colloidal characteristics, when injected intradermally to a mouse model of lymph node metastasis, DFNP could produce reliable ratiometric signals to provide information on the MMP-2,9 activity in the lymph nodes depending on metastatic progression, which corresponded well to the temporal histologic analysis. Furthermore, ratiometric lymph node imaging with DFNP after photodynamic therapy allowed for monitoring a therapeutic response to the given cancer treatment, demonstrating diagnostic and prognostic potential of the nanoconstructed colloidal sensor of tumor microenvironment in cancer treatment.",
keywords = "Cancer diagnosis, Dual-channel fluorescence imaging, Fluorogenic nanoprobe, Lymph node metastasis, Matrix metalloproteinase-2,9",
author = "Cho, {Hong Jun} and Seokyung Lee and Park, {Sung Jun} and Lee, {Yong Deok} and Keunsoo Jeong and Park, {Jae Hyung} and Lee, {Yoon Sik} and Bokyung Kim and Jeong, {Han Sin} and Sehoon Kim",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.colsurfb.2019.03.047",
language = "English",
volume = "179",
pages = "9--16",
journal = "Colloids and Surfaces B: Biointerfaces",
issn = "0927-7765",
publisher = "Elsevier",

}

TY - JOUR

T1 - Tumor microenvironment-responsive fluorogenic nanoprobe for ratiometric dual-channel imaging of lymph node metastasis

AU - Cho, Hong Jun

AU - Lee, Seokyung

AU - Park, Sung Jun

AU - Lee, Yong Deok

AU - Jeong, Keunsoo

AU - Park, Jae Hyung

AU - Lee, Yoon Sik

AU - Kim, Bokyung

AU - Jeong, Han Sin

AU - Kim, Sehoon

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Fluorogenic nanoprobes capable of providing microenvironmental information have extensively been developed to improve the diagnostic accuracy for early or metastatic cancer detection. In cancer-associated microenvironment, matrix metalloproteinase-2,9 (MMP-2,9) has drawn attention as a representative enzymatic marker for diagnosis, prognosis, and prediction of various cancers, which is overexpressed in the primary site as well as metastatic regions. Here, we devised dual-emissive fluorogenic nanoprobe (DFNP) emitting both MMP-2,9-sensitive and insensitive fluorescence signals, for accurate monitoring of the MMP-2,9 activity in metastatic regions. DFNP was nanoscopically constructed by amphiphilic self-assembly between a constantly fluorescent polymer surfactant labeled with Cy7 (F127-Cy7) and an initially nonfluorescent hydrophobic peptide (Cy5.5-MMP-Q) that is fluorogenic in response to MMP-2,9. Ratiometric readout (Cy5.5/Cy7) by dual-channel imaging could normalize the enzyme-responsive sensing signal relative to the constantly emissive internal reference that reflects the probe amount, allowing for semi-quantitative analysis on the MMP-2,9-related tissue microenvironment. In addition to the dual-channel emission, the nanoconstructed colloidal structure of DFNP enabled efficient accumulation to lymph node in vivo. Because of these two colloidal characteristics, when injected intradermally to a mouse model of lymph node metastasis, DFNP could produce reliable ratiometric signals to provide information on the MMP-2,9 activity in the lymph nodes depending on metastatic progression, which corresponded well to the temporal histologic analysis. Furthermore, ratiometric lymph node imaging with DFNP after photodynamic therapy allowed for monitoring a therapeutic response to the given cancer treatment, demonstrating diagnostic and prognostic potential of the nanoconstructed colloidal sensor of tumor microenvironment in cancer treatment.

AB - Fluorogenic nanoprobes capable of providing microenvironmental information have extensively been developed to improve the diagnostic accuracy for early or metastatic cancer detection. In cancer-associated microenvironment, matrix metalloproteinase-2,9 (MMP-2,9) has drawn attention as a representative enzymatic marker for diagnosis, prognosis, and prediction of various cancers, which is overexpressed in the primary site as well as metastatic regions. Here, we devised dual-emissive fluorogenic nanoprobe (DFNP) emitting both MMP-2,9-sensitive and insensitive fluorescence signals, for accurate monitoring of the MMP-2,9 activity in metastatic regions. DFNP was nanoscopically constructed by amphiphilic self-assembly between a constantly fluorescent polymer surfactant labeled with Cy7 (F127-Cy7) and an initially nonfluorescent hydrophobic peptide (Cy5.5-MMP-Q) that is fluorogenic in response to MMP-2,9. Ratiometric readout (Cy5.5/Cy7) by dual-channel imaging could normalize the enzyme-responsive sensing signal relative to the constantly emissive internal reference that reflects the probe amount, allowing for semi-quantitative analysis on the MMP-2,9-related tissue microenvironment. In addition to the dual-channel emission, the nanoconstructed colloidal structure of DFNP enabled efficient accumulation to lymph node in vivo. Because of these two colloidal characteristics, when injected intradermally to a mouse model of lymph node metastasis, DFNP could produce reliable ratiometric signals to provide information on the MMP-2,9 activity in the lymph nodes depending on metastatic progression, which corresponded well to the temporal histologic analysis. Furthermore, ratiometric lymph node imaging with DFNP after photodynamic therapy allowed for monitoring a therapeutic response to the given cancer treatment, demonstrating diagnostic and prognostic potential of the nanoconstructed colloidal sensor of tumor microenvironment in cancer treatment.

KW - Cancer diagnosis

KW - Dual-channel fluorescence imaging

KW - Fluorogenic nanoprobe

KW - Lymph node metastasis

KW - Matrix metalloproteinase-2,9

UR - http://www.scopus.com/inward/record.url?scp=85063495286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063495286&partnerID=8YFLogxK

U2 - 10.1016/j.colsurfb.2019.03.047

DO - 10.1016/j.colsurfb.2019.03.047

M3 - Article

VL - 179

SP - 9

EP - 16

JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

SN - 0927-7765

ER -