Inorganic nanocarriers for siRNA delivery for cancer treatments

Abstract

RNA interference is one of the emerging methodologies utilized in the treatment of a wide variety of diseases including cancer. This method specifically uses therapeutic RNAs (TpRNAs) like small interfering RNAs (siRNAs) to regulate/silence the cancer-linked genes, thereby minimizing the distinct activities of the cancer cells while aiding in their apoptosis. But, many complications arise during the transport/delivery of these TpRNAs that include poor systemic circulation, instability/degradation inside the body environment, no targeting capacity and also low cellular internalization. These difficulties can be overcome by using nanocarriers to deliver the TpRNAs inside the cancer cells. The following are the various categories of nanocarriers-viral vectors (e.g. lentivirus and adenovirus) and non-viral nanocarriers (self-assembling nanocarriers and inorganic nanocarriers). Viral vectors suffer from disadvantages like high immunogenicity compared to the non-viral nanocarriers. Among non-viral nanocarriers, inorganic nanocarriers gained significant attention as their inherent properties (like magnetic properties) can aid in the effective cellular delivery of the TpRNAs. Most of the prior reports have discussed about the delivery of TpRNAs through self-assembling nanocarriers; however very few have reviewed about their delivery using the inorganic nanoparticles. Therefore, in this review, we have mainly focussed on the delivery of TpRNAs-i.e. siRNA, especially programmed death ligand-1 (PD-L1), survivin, B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor and other siRNAs using the inorganic nanoparticles-mainly magnetic, metal and silica nanoparticles. Moreover, we have also discussed about the combined delivery of these TpRNAs along with chemotherapeutic drugs (mainly doxorubicin) andin vitroandin vivotherapeutic effectiveness.

Keywords: Bcl-2 and VEGF; PD-L1; cancer treatment; chemotherapy; magnetic/metal/silica nanoparticles; siRNA; survivin.