Engineering oncogene-targeted anisamide-functionalized pBAE nanoparticles as efficient lung cancer antisense therapies.

Non-small cell lung cancer (NSCLC) is one of the leading causes of worldwide death, mainly due to the lack of efficient and safe therapies. Currently, NSCLC standard of care for consist on the use of traditional chemotherapeutics, non-selectively distributed through the whole body, thus causing severe side effects while not achieving high efficacy outcomes. Consequently, the need of novel therapies, targeted to modify specific subcellular routes aberrantly expressed only in tumor cells is still urgent. In this context, the delivery of siRNAs that can know-down overexpressed oncogenes, such as mTOR, could become the promised targeted therapy. However, siRNA effective delivery remains a challenge due to its compromised stability in biological fluids and its inability to cross biological and plasmatic membranes. Therefore, polymeric nanoparticles that efficiently encapsulate siRNAs and are selectively targeted to tumor cells could play a pivotal role. Accordingly, we demonstrate in this work that oligopeptide end-modified poly(beta aminoester) (OM-pBAE) polymers can efficiently complex siRNA in small nanometric particles using very low polymer amounts, protecting siRNA from nucleases attack. These nanoparticles are stable in the presence of serum, advantageous fact in terms of