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

doi:10.1016/j.colsurfb.2019.03.047

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^*

^*Corresponding author for this work

KU-KIST Graduate School of Converging Science and Technology

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

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 language	English
Pages (from-to)	9-16
Number of pages	8
Journal	Colloids and Surfaces B: Biointerfaces
Volume	179
DOIs	https://doi.org/10.1016/j.colsurfb.2019.03.047
Publication status	Published - 2019 Jul 1

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea ( 2017M3A9D8029942 , and 2014M3C1A3054141 ), the Korea Health Industry Development Institute ( HI15C1540 ), the Development of Platform Technology for Innovative Medical Measurements Program from Korea Research Institute of Standards and Science ( KRISS-2018-GP2018-0018 ), and the Intramural Research Program of KIST.

Publisher Copyright:
© 2019 Elsevier B.V.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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

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10.1016/j.colsurfb.2019.03.047

Cite this

@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",

note = "Funding Information: This work was supported by grants from the National Research Foundation of Korea ( 2017M3A9D8029942 , and 2014M3C1A3054141 ), the Korea Health Industry Development Institute ( HI15C1540 ), the Development of Platform Technology for Innovative Medical Measurements Program from Korea Research Institute of Standards and Science ( KRISS-2018-GP2018-0018 ), and the Intramural Research Program of KIST. Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

year = "2019",

month = jul,

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 B.V.",

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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

N1 - Funding Information: This work was supported by grants from the National Research Foundation of Korea ( 2017M3A9D8029942 , and 2014M3C1A3054141 ), the Korea Health Industry Development Institute ( HI15C1540 ), the Development of Platform Technology for Innovative Medical Measurements Program from Korea Research Institute of Standards and Science ( KRISS-2018-GP2018-0018 ), and the Intramural Research Program of KIST. Publisher Copyright: © 2019 Elsevier B.V.

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

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DO - 10.1016/j.colsurfb.2019.03.047

M3 - Article

C2 - 30928802

AN - SCOPUS:85063495286

SN - 0927-7765

VL - 179

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JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

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