Background: Cancer poses a major public health issue, is linked with high mortality rates across the
world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics,
including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment,
although diverse obstacles for achieving the permanent “magic bullet” cure have remained. Recently, various
anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments
have received considerable attention. One of these promising and novel agents is the siRNA delivery system;
however, poor cellular uptake and altered siRNA stability in physiological environments have limited its use in
clinical trials. Therefore, developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA
stability in the body’s circulation, and prevention of its rapid clearance from bodily fluids, is rapidly emerging as
an innovative therapeutic strategy to combat cancer. Moreover, active targeting using ligand moieties which bind
to over-expressed receptors on the surface of cancer cells would enhance the therapeutic efficiency of siRNA.
Conclusion: In this review, we provide 1) an overview of the non-viral carrier associated with siRNA delivery for
cancer treatment, and 2) a description of the five major cancer-targeting ligands.