Nanotechnology-based siRNA delivery strategies for metastatic colorectal cancer therapy

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world, mainly due to distant metastases events. The metastatic CRC (mCRC) stages are resistant to the therapeutic recommended. Therefore, it urges the development of more efficient strategies to impair the disease. Small interfering RNA (siRNA) is a well-known silencing tool with impact on targeted cancer therapy, even though in vivo challenges difficult its clinical application. Here, multiple solutions to overcome the extracellular and intracellular barriers encountered by intravenous delivery of siRNA are discussed. Moreover, it is emphasized the association of siRNA with nanoparticles to enable the long-term release and to counteract the toxicity issues of siRNA. Particular attention is paid on the potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles for systemic siRNA delivery in mCRC. Despite of being less used so far due to technological difficulties, multiple strategies to successfully encapsulate siRNA into PLGA nanocarriers are summarized.