Nanoscale-based delivery of RNAi for cancer therapy

The ability to detect pathways that malignant tissue depends on, combined with the specific gene-knockdown ability of siRNA/miRNA, may revolutionize cancer treatment. The capability of providing personalized care to cancer patients allows therapy to be specifically tailored for each case. Several studies of malignant and nonmalignant tissues have been performed in the context of global protein interaction networks in order to find the optimal targets, providing a list of potential gene and protein targets for each cancer type and for each patient. Nevertheless, due to poor stability of RNAi molecules in physiological conditions and its inability to cross cellular membranes, the in vivo delivery of siRNA and miRNA holds a great challenge and remains a crucial issue for its therapeutic success. Supramolecular carriers are often used in order to improve the physicochemical and biopharmaceutical properties of RNAi. Nanoscale drug delivery systems will enable the accumulation of the drugs in the tumors due to the enhanced permeability and retention (EPR) effect, and release the siRNA/miRNA only inside the target cell. In addition, a targeting moiety can increase the selectivity and specific uptake in the target tissue. Several vehicles (dendrimers, nanoparticles, polyplex, lipoplex, polymeric nanoconjugates) are being developed for siRNA/miRNA delivery. These vehicles provide an important tool for exploiting the full potential of nucleic acids as therapeutic agents. In this chapter, we will review the different approaches to deliver oligonucleotides in vivo.