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

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.