Towards targeting of a ROS-responsive nanomedicine to the tumor microenvironment

MARÍA ELENA IEZZI; SANTIAGO WERBAHJ; MILENA BATALLA; OSVALDO PODHAJCER; LUCÍA POLICASTRO; GABRIELA CANZIANI

Buenos Aires

Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine South American Group (VIII SFRBM-SAG) VIII. 2013, RA; 2013

Accumulating evidence indicates that the tumor microenvironment produces higher ROS levels compared to normal organs. In a previous work, we had developed a novel, advanced medicinal therapeutic product based on a non viral vector where a ROS-responsive, synthetic, chimeric promoter drives the expression of therapeutic genes named E6(40)VE-TK. This product is useful for direct intra-tissue administration. We describe here the buiding of a nanovehicle designed to improve its delivery systemically. We prepared stealth liposomes of 100-120 nm of diameter with 4% PEG. We have evaluated the encapsulation of the DNA-based vector by several methods. We obtained 80-90% encapsulation using 10 cycles of freezing and thawing combined with the use of the injection ethanol method. Further we conjugated a tumor antigen-targeted antibody to the vector loaded-liposome to retarget the nanoparticle. We were able to attach 20-35 Fab´ molecules per liposome. In future studies we will evaluate the therapeutic efficacy of this nanomedicine.