1. Academic Validation
  2. Synthesis and Biological Evaluation of New Fluorescent Probe BPN-01: A Model Molecule for Fluorescence Image-guided Surgery

Synthesis and Biological Evaluation of New Fluorescent Probe BPN-01: A Model Molecule for Fluorescence Image-guided Surgery

  • J Fluoresc. 2023 Sep;33(5):1827-1839. doi: 10.1007/s10895-023-03166-7.
Hendris Wongso # 1 2 Hanna Goenawan 3 4 5 Ronny Lesmana # 3 4 5 Isa Mahendra # 6 7 Ahmad Kurniawan 6 Teguh H A Wibawa 6 Witri Nuraeni 8 Endah Rosyidiah 8 Yanuar Setiadi 9 Nova Sylviana 3 4 5 Yuni Susanti Pratiwi 3 4 5 Aziiz Mardanarian Rosdianto 3 4 5 10 Unang Supratman 11 Crhisterra E Kusumaningrum 6
Affiliations

Affiliations

  • 1 Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia. hend042@brin.go.id.
  • 2 Research Collaboration Center for Theranostic Radiopharmaceuticals, National Research and Innovation Agency, Jl. Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia. hend042@brin.go.id.
  • 3 Department of Biomedical Science, Physiology Division, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Indonesia.
  • 4 Physiology Molecular, Division of Biological Activity, Central Laboratory, Universitas Padjadjaran, Jatinangor, 45363, Indonesia.
  • 5 Laboratory of Sciences, Graduate School, Universitas Padjadjaran, Bandung, Indonesia.
  • 6 Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia.
  • 7 Research Collaboration Center for Theranostic Radiopharmaceuticals, National Research and Innovation Agency, Jl. Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia.
  • 8 Directorate of Laboratory Management, Research Facilities, and Science and Technology Park, National Research and Innovation Agency of Indonesia, Jl. Tamansari No. 71, Lb. Siliwangi, Bandung, West Java, 40132, Indonesia.
  • 9 Research Organization for Life Sciences and Environment, Research Center for Environmental and Clean Technology, National Research and Innovation Agency, Puspiptek, Banten, 15314, Indonesia.
  • 10 Veterinary Medicine Study Program, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Indonesia.
  • 11 Departement of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km 21, Jatinangor, 45363, Indonesia.
  • # Contributed equally.
Abstract

Fluorescence image-guided surgery (FIGS) can serve as a tool to achieve successful resection of tumour tissues during surgery, serving as a surgical navigator for surgeons. FIGS relies on the use of fluorescent molecules that can specifically interact with Cancer cells. In this work, we developed a new model of fluorescent probe based on benzothiazole-phenylamide moiety featuring the visible fluorophore nitrobenzoxadiazole (NBD), namely BPN-01. This compound was designed and synthesised for potential applications in the tissue biopsy examination and ex-vivo imaging during FIGS of solid cancers. The probe BPN-01 exhibited favourable spectroscopic properties, particularly in nonpolar and alkaline Solvents. Moreover, in vitro fluorescence imaging revealed that the probe appeared to recognise and be internalised in the prostate (DU-145) and melanoma (B16-F10) Cancer cells, but not in the normal cells (myoblast C2C12). The cytotoxicity studies revealed that probe BPN-01 was not toxic to the B16 cells, suggesting excellent biocompatibility. Furthermore, the computational analysis showed that the calculated binding affinity of the probe to both translocator protein 18 kDa (TSPO) and human epidermal growth factor receptor 2 (HER2) was considerably high. Hence, probe BPN-01 displays promising properties and may be valuable for visualising Cancer cells in vitro. Furthermore, ligand 5 can potentially be labelled with NIR fluorophore and radionuclide, and serves as a dual imaging agent for in vivo applications.

Keywords

Benzothiazole-phenylamide; Cancer imaging; Fluorescence image-guided surgery; Fluorescent probe BPN-01; Nitrobenzoxadiazole (NBD).

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