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
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
UR - http://www.scopus.com/inward/record.url?scp=85063495286&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2019.03.047
DO - 10.1016/j.colsurfb.2019.03.047
M3 - Article
C2 - 30928802
AN - SCOPUS:85063495286
SN - 0927-7765
VL - 179
SP - 9
EP - 16
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -
