Malaria Biomimetic for Tumor Targeted Drug Delivery
Jessica Pihl, Thomas Mandel Clausen, Jiarong Zhou, Nishta Krishnan, Maj Sofie Ørum-Madsen, Tobias Gustavsson, Robert Dagil, Mads Daugaard, Swati Choudhary, Camilla Foged, Jeffrey D. Esko, Liangfang Zhang, Ronnie H. Fang, Ali Salanti
Abstract
Malaria infected erythrocytes utilize the parasite protein VAR2CSA to bind to a unique presentation of chondroitin sulfate (CS) for their placenta specific tropism. Interestingly, many cancers express a similar form of CS, thereby termed oncofetal CS (ofCS). The distinctive tropism of malaria infected erythrocytes and the identification of oncofetal CS, therefore, represent potentially potent tools for cancer targeting. Here we describe an intriguing drug delivery platform that effectively mimics infected erythrocytes and their specificity for ofCS. We used a lipid catcher-tag conjugation system for the functionalization of erythrocyte membrane-coated drug carriers with recombinant VAR2CSA (rVAR2). We show that these malaria mimicking erythrocyte nanoparticles (MMENPs) loaded with docetaxel (DTX) specifically target and kill melanoma cells in vitro . We further demonstrate effective targeting and therapeutic efficacy in a xenografted melanoma model. These data thus provide a proof of concept for the use of a malaria biomimetic for tumor targeted drug delivery. Given the broad presentation of ofCS found across various types of malignancies, this biomimetic may therefore show potential as a broadly targeted cancer therapy against multiple tumor indications.