ICRS 2018

Image-guided surgery using near-infrared Turn-ON nanoprobes improves tumor-free survival

Rachel Blau 1 Yana Epshtein 1 Evgeni Pisarevsky 1 Galia Tiram 1 Sahar Israeli Dangoor 1 Eilam Yeini 1 Adva Krivitsky 1 Anat Eldar-Boock 1 Dikla Ben-Shushan 1 Hadas Gibori 1 Anna Scomparin 1 Ori Green 2 Yael Ben-Nun 3 Emmanuelle Merquiol 3 Hila Doron 4 Galia Blum 3 Neta Erez 4 Rachel Grossman 5 Zvi Ram 5 Doron Shabat 2 Ronit Satchi-Fainaro 1
1Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2Department of Organic Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
3School of Pharmacy, The Institute for Drug Research, Faculty of Medicine, Campus Ein Kerem, The Hebrew University of Jerusalem, Jerusalem, Israel
4Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel

Complete tumor removal during surgery has a great impact on patient prognosis and survival. In order to remove the tumor tissue completely with minimal collateral damage to healthy tissue, there is a need for diagnostic tools that will differentiate between the tumor and its healthy surroundings1.

We present here the design, synthesis and characterization of a novel polymeric Turn-ON probe that is enzymatically degraded by cysteine cathepsins to generate a fluorescence signal. This polymeric Turn-ON probe was recently reported by us2 and composed of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer bearing self-quenched Cy5 fluorescent dyes. We studied the kinetics of the polymeric nano-probe on orthotopic breast cancer model in mice and showed a high tumor-to-background ratio. The signal obtained from the tumor was stable and delineated the tumor boundaries during the whole surgical procedure, enabling an accurate resection. The control groups which underwent standard surgery under white light only, or under the fluorescence guidance of the commercially-available probes ProSense® 680 or 5-Aminolevulinic acid (5-ALA) survived less time and suffered from tumor recurrence earlier than the group that underwent image-guided surgery using our Turn-ON probes3.

Our “smart” polymeric Turn-ON probe can potentially assist surgeons to decide in real time during surgery regarding the tumor margins needed to be removed, leading to improved patient outcome.

References

  1. Blau R, Krivitsky A, Epshtein Y, Satchi-Fainaro R. Are nanotheranostics and nanodiagnostics-guided drug delivery stepping stones towards precision medicine? Drug Resist Update. Jul 2016;27:39-58.
  2. Ferber S, Baabur-Cohen H, Blau R, et al. Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release. Cancer Lett. Mar 2014; 352(1): 81-89.
  3. Blau R, Epshtein Y, Pisarevsky E, et al. Image-Guided Surgery Using Near Infrared Turn-ON Fluorescent Nanoprobes for Precise Detection of Tumor Margins, Theranostics. Jun 2018; 8(13):3437-3460.








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