Glutathione/pH-responsive nanosponges enhance strigolactone delivery to prostate cancer cells

// Monica Argenziano 1 , Chiara Lombardi 2 , Benedetta Ferrara 1 , Francesco Trotta 2 , Fabrizio Caldera 2 , Marco Blangetti 2 , Hinanit Koltai 3 , Yoram Kapulnik 3 , Ronit Yarden 4 , Luca Gigliotti 5 , Umberto Dianzani 5 , Chiara Dianzani 1 , Cristina Prandi 2 and Roberta Cavalli 1 1 Department of Drug Science and Technology, University of Turin, Turin, Italy 2 Department of Chemistry, University of Turin, Turin, Italy 3 Agricultural Research Organization, Volcani Center, Rishon LeTsiyon, Israel 4 Georgetown University Medical Center, Washington DC, USA 5 Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy Correspondence to: Roberta Cavalli, email: roberta.cavalli@unito.it Keywords: strigolactones; GSH/pH-responsive nanosponges; prostate cancer cells; controlled release; intracellular delivery Received: December 28, 2017      Accepted: October 24, 2018      Published: November 09, 2018 ABSTRACT Strigolactones (SLs) are carotenoid-derived plant hormones that exhibit anti-cancer activities. We previously demonstrated that two SL analogues, MEB55 and ST362, inhibit the growth and survival of various cancer cell lines. However, these compounds have low aqueous solubility and stability at physiological pH. Here, we generated SL-loaded glutathione/pH-responsive nanosponges (GSH/pH-NS) to selectively deliver SLs to prostate cancer cells and enhance their therapeutic efficacy. The SLs were readily incorporated into the GSH/pH-NS. The drug loading efficiency was 13.9% for MEB55 and 15.4% for ST362, and the encapsulation efficiency was 88.7% and 96.5%, respectively. Kinetic analysis revealed that release of MEB55 and ST362 from the GSH/pH-NS was accelerated at acidic pH and in the presence of a high GSH concentration. Evaluation of the effects of MEB55- and ST362-loaded GSH/pH-NS on the growth of DU145 (high GSH) and PC-3 (low GSH) prostate cancer cells revealed that the GSH/pH-NS inhibited the proliferation of DU145 cells to a greater extent than free MEB55 or ST362 over a range of concentrations. These findings indicate GSH/pH-NS are efficient tools for controlled delivery of SLs to prostate cancer cells and may enhance the therapeutic efficacy of these compounds.