TY - JOUR
T1 - Nanoparticle Formulation of Indocyanine Green Improves Image-Guided Surgery in a Murine Model of Breast Cancer
AU - Wojtynek, Nicholas E.
AU - Olson, Madeline T.
AU - Bielecki, Timothy A.
AU - An, Wei
AU - Bhat, Aaqib M.
AU - Band, Hamid
AU - Lauer, Scott R.
AU - Silva-Lopez, Edibaldo
AU - Mohs, Aaron M.
N1 - Funding Information:
This work was supported in part by the National Institutes of Health grants, R01EB019449, P50CA127297, P20GM103480, 1S10RR17846, 1S10RR027940, and P30CA036727 (Fred and Pamela Buffett Cancer Center at UNMC), Department of Defense Breast Cancer Research Program grant (W81XWH-14-1-0567), and the Nebraska Research Initiative. NEW would like to thank the UNMC Graduate Studies Assistantship/Fellowship and the John Borrlson Memorial Scholarship for support. We would also like to thank Megan Holmes, Freshta Baher, Xiaoxiao Qi, and Melissa Malone for technical assistance. Finally, we would like to thank the UNMC Flow Cytometry Core Facilities for assistance with flow sorting analysis, UNMC Small Animal Imaging Core Facility for access to IVIS, UNMC Tissue Sciences Core Facility for sectioning and staining of breast cancer tissue, and UNMC Comparative Medicine Personnel (Kristin Leland and Wendy Schwendeman) for assistance with animal protocol development.
Funding Information:
This work was supported in part by the National Institutes of Health grants, R01EB019449, P50CA127297, P20GM103480, 1S10RR17846, 1S10RR027940, and P30CA036727 (Fred and Pamela Buffett Cancer Center at UNMC), Department of Defense Breast Cancer Research Program grant (W81XWH-14-1-0567), and the Nebraska Research Initiative. NEW would like to thank the UNMC Graduate Studies Assistantship/Fellowship and the John Borrlson Memorial Scholarship for support. We would also like to thank Megan Holmes, Freshta Baher, Xiaoxiao Qi, and Melissa Malone for technical assistance. Finally, we would like to thank the UNMC Flow Cytometry Core Facilities for assistance with flow sorting analysis, UNMC Small Animal Imaging Core Facility for access to IVIS, UNMC Tissue Sciences Core Facility for sectioning and staining of breast cancer tissue, and UNMC Comparative Medicine Personnel (Kristin Leland and Wendy Schwendeman) for assistance with animal protocol development.
Publisher Copyright:
© 2019, World Molecular Imaging Society.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Purpose: Negative surgical margins (NSMs) have favorable prognostic implications in breast tumor resection surgery. Fluorescence image-guided surgery (FIGS) has the ability to delineate surgical margins in real time, potentially improving the completeness of tumor resection. We have recently developed indocyanine green (ICG)-loaded self-assembled hyaluronic acid (HA) nanoparticles (NanoICG) for solid tumor imaging, which were shown to enhance intraoperative contrast. Procedures: This study sought to assess the efficacy of NanoICG on completeness of breast tumor resection and post-surgical survival. BALB/c mice bearing iRFP+/luciferase+ 4T1 syngeneic breast tumors were administered NanoICG or ICG, underwent FIGS, and were compared to bright light surgery (BLS) and sham controls. Results: NanoICG increased the number of complete resections and improved tumor-free survival. This was a product of improved intraoperative contrast enhancement and the identification of a greater number of small, occult lesions than ICG and BLS. Additionally, NanoICG identified chest wall invasion and predicted recurrence in a model of late-stage breast cancer. Conclusions: NanoICG is an efficacious intraoperative contrast agent and could potentially improve surgical outcomes in breast cancer.
AB - Purpose: Negative surgical margins (NSMs) have favorable prognostic implications in breast tumor resection surgery. Fluorescence image-guided surgery (FIGS) has the ability to delineate surgical margins in real time, potentially improving the completeness of tumor resection. We have recently developed indocyanine green (ICG)-loaded self-assembled hyaluronic acid (HA) nanoparticles (NanoICG) for solid tumor imaging, which were shown to enhance intraoperative contrast. Procedures: This study sought to assess the efficacy of NanoICG on completeness of breast tumor resection and post-surgical survival. BALB/c mice bearing iRFP+/luciferase+ 4T1 syngeneic breast tumors were administered NanoICG or ICG, underwent FIGS, and were compared to bright light surgery (BLS) and sham controls. Results: NanoICG increased the number of complete resections and improved tumor-free survival. This was a product of improved intraoperative contrast enhancement and the identification of a greater number of small, occult lesions than ICG and BLS. Additionally, NanoICG identified chest wall invasion and predicted recurrence in a model of late-stage breast cancer. Conclusions: NanoICG is an efficacious intraoperative contrast agent and could potentially improve surgical outcomes in breast cancer.
KW - Breast Cancer
KW - Fluorescence image-guided surgery
KW - Hyaluronic acid
KW - Indocyanine green
KW - Nanoparticle
KW - Near infrared fluorescence
UR - http://www.scopus.com/inward/record.url?scp=85076755825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076755825&partnerID=8YFLogxK
U2 - 10.1007/s11307-019-01462-y
DO - 10.1007/s11307-019-01462-y
M3 - Article
C2 - 31820350
AN - SCOPUS:85076755825
VL - 22
SP - 891
EP - 903
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
SN - 1536-1632
IS - 4
ER -