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

IEZZI ME; WERBAJH S; BATALLA M; CANZIANI G; PODHAJCER O; POLICASTRO L

Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine-South American Group; 2013

Accumulating evidence indicate that the tumor microenvironment produce higher ROS levels compared to normal organs. In a previous work, we have 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 (Policastro et al, 2009, 2012). In this work we decided to develope a nanovehicle for improving its delivery systemically. We obtained stealth liposomes of 100-120 nm of diameter that contain 4% PEG. We have evaluated the encapsulation of the DNA-based vector by several methods. We obtained 90-100% encapsulation using 10 cycles of frreezing 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 35-20 Fab´ molecules per liposome. In future studies we will evaluate the therapeutic efficacy of this nanomedicine.