Recently, investigations have revealed that RNA interference (RNAi) has a remarkable potential to decrease cancer burden by downregulating genes. Among various RNAi molecules, small interfering RNA (siRNA) has been more attractive for this goal and is able to silence a target pathological path and promote the degradation of a certain mRNA, resulting in either gain or loss of function of proteins. Moreover, therapeutic siRNAs have exhibited low side effects compared to other therapeutic molecular candidates. Nevertheless, siRNA delivery has its own limitations including quick degradation in circulation, ineffective internalization and low passive uptake by cells, possible toxicity against off-target sites, and inducing unfavorable immune responses. Therefore, delivery tools must be able to specifically direct siRNAs to their target locations without inflicting detrimental effects on other sites. To conquer the mentioned problems, nanocarrier-mediated delivery of siRNAs, using inorganic nanoparticles (NPs), polymers, and lipids, has been developed as a biocompatible delivery approach. In this review, we have discussed recent advances in the siRNA delivery methods that employ nanoparticles, lipids, and polymers, as well as the inorganic-based co-delivery systems used to deliver siRNAs and anticancer agents to target cells.
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