Emerging nanodelivery strategies of RNAi molecules for colon cancer therapy: preclinical developments

Although local colonic delivery is achievable through several strategies, colon cancer is still considered one of the leading causes of death worldwide. Failure of chemotherapeutics to exhibit efficient anticancer activity might be attributed to the development of multidrug resistance (MDR) mechanisms including the overexpression of certain oncogenes such as MDR1/P-gp. One of the major reasons for the shortcoming of P-gp inhibitors in clinic is the nonspecific distribution of them to nontarget organs, which leads to reduced elimination and increased toxicity of its substrates including anticancer agents. Numerous studies have demonstrated the effectiveness of gene-silencing approaches in reversing the P-gp-mediated MDR. However, none have reached clinical trials yet. Several drug-delivery systems have been investigated primarily to address P-gp and the observed improved anticancer efficacy suggests that nanomedicine provides new opportunities to overcome MDR in cancer. In this review, novel therapeutic strategies for colon cancer therapy will be discussed in the context of P-gp inhibition by low-molecular-weight agents and RNAi molecules.