@article{5779ddf997944e1ea162f7f49af003c0,
title = "Nanobodies Targeting Prostate-Specific Membrane Antigen for the Imaging and Therapy of Prostate Cancer",
abstract = "The repertoire of methods for the detection and chemotherapeutic treatment of prostate cancer (PCa) is currently limited. Prostate-specific membrane antigen (PSMA) is overexpressed in PCa tumors and can be exploited for both imaging and drug delivery. We developed and characterized four nanobodies that present tight and specific binding and internalization into PSMA+ cells and that accumulate specifically in PSMA+ tumors. We then conjugated one of these nanobodies to the cytotoxic drug doxorubicin, and we show that the conjugate internalizes specifically into PSMA+ cells, where the drug is released and induces cytotoxic activity. In vivo studies show that the extent of tumor growth inhibition is similar when mice are treated with commercial doxorubicin and with a 42-fold lower amount of the nanobody-conjugated doxorubicin, attesting to the efficacy of the conjugated drug. These data highlight nanobodies as promising agents for the imaging of PCa tumors and for the targeted delivery of chemotherapeutic drugs. ",
author = "Lior Rosenfeld and Amiram Sananes and Yuval Zur and Shira Cohen and Kalyan Dhara and Sigal Gelkop and {Ben Zeev}, Efrat and Anat Shahar and Leslie Lobel and Barak Akabayov and Eyal Arbely and Niv Papo",
note = "Funding Information: We thank Prof. Serge Muyldermans and Dr. Cecile Vincke for providing the protocols for animal immunization and nanobody screening assay. We thank Dr. Alon Zilka for his technical assistance. SPR and microscopy experiments were performed at the NIBN Proteomics, Cytometry and Microscopy unit. We thank Prof. Varda Shoshan-Barmatz and Dr. Srinivas Pittala from Ben-Gurion University for the assistance with histology. The structural studies were performed on beamlines ID30-A3 and ID30-B at the European Synchrotron Radiation Facility (ESRF), Grenoble, France. We are grateful to the beamline scientists for providing assistance in using these beamlines. We thank the staff from the BM29-BioSAXS Beamline of the European Synchrotron Facility in Grenoble (ESRF). This work was supported by the European Research Council “Ideas Program” ERC-2013-StG (Grant 336041) and the Prostate Cancer Foundation (PCF) to N.P. Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",
year = "2020",
month = jul,
day = "23",
doi = "10.1021/acs.jmedchem.0c00418",
language = "English",
volume = "63",
pages = "7601--7615",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "14",
}
