Nanobodies Targeting Prostate-Specific Membrane Antigen for the Imaging and Therapy of Prostate Cancer

Lior Rosenfeld, Amiram Sananes, Yuval Zur, Shira Cohen, Kalyan Dhara, Sigal Gelkop, Efrat Ben Zeev, Anat Shahar, Leslie Lobel, Barak Akabayov, Eyal Arbely, Niv Papo

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)7601-7615
Number of pages15
JournalJournal of Medicinal Chemistry
Issue number14
Early online date22 May 2020
StatePublished - 23 Jul 2020

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery


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