PO-429 Elastin-like recombinamers nanoparticles: an effective drug delivery system on colorectal cancer cells

Abstract

IntroductionWith almost 1,4 million new cases each year worldwide, colorectal cancer kills 228.000 Europeans every year. Although new therapies have been discovered, the use of recombinant elastin-based biomaterials could open a new approach in cancer research as polymeric carriers for drug delivery in order to improve the accuracy of the action and reduce the toxicity of chemotherapeutic agents. In this work, we have developed a new elastin-like recombinamer (ELR) fused to a peptide inhibitor of the protein kinase Akt. This polymer self-assembled into nanoparticles, which showed killing ability on colorectal cancer cells (Caco-2).Material and methodsTaking advantage of the recombinant DNA technology, the constructs were formed by an amphiphilic backbone and several bioactive sequences, with an Akt inhibitor among others. ELR were produced by E. coli fermentation and, after purification process, were characterised and tested in vitro. Cellular viability assays on cancerous cells were carried out in order to study the killing ability of these nanoparticles.Results and discussionsBoth physical and chemical characterisation of this novel ELR showed that it is able to self-assemble into nanoparticles with a diameter of 68 nm, which are an effective way to deliver the Akt inhibitor into the cytoplasm, where it will bind to its protein target Akt and stop the kinase activity. With a transition temperature of 18°C and a high negatively-charged surface, nanoparticles perfectly met all requirements for its use as biomedical tools. Moreover, nanoparticles showed increased killing ability on cancerous cells compared to non-cancerous cells.ConclusionThus, we have designed a new system able to enter into the cancerous cells and inhibit Akt signalling pathway. As an interesting advantage, ELRs have the ability to be modified by adding different molecules, such as aptamers or single chain antibodies, in order to be selectively targeted against cancerous cells. Thus, the action of these nanoparticles will be more accurate so as to achieve a new therapeutic tool for colorectal cancer treatment.