Abstract
Multidrug resistance (MDR) is a major obstacle in the successful treatment of human cancer. Experimental evidence from multiple laboratories implicates a wide range of mechanisms including over-expression of multidrug resistance 1 gene (MDR-1) and antiapoptotic genes that contribute to the drug resistant phenotype. Reversing MDR has been a high priority goal of clinical and investigational oncology, but still remains elusive. RNA interference (RNAi) has emerged as a powerful tool for sequence-specific gene silencing strategy. RNAi can be achieved by using small interfering RNA (siRNA) for target gene silencing in tumor cells. Synthetic, plasmid-based siRNA, and viral-based short hairpin RNA (shRNA) can significantly block MDR-1 and antiapoptotic gene expressions in drug resistant tumor cells. Although the RNAi technology is an excellent candidate to reverse MDR in cancer therapy, several serious challenges remain including unstable and rapid degradation by systemic and cellular nuclei and poor membrane permeability of siRNA for routine clinical application. Nanotechnology-based systems have been developed to deliver a variety of therapeutic agents, including nucleic acid constructs, into specific cells. Nanoparticulate formulations have recently emerged as alternatives to plasmid or viral vectors for the delivery of siRNA. This review summarizes current developments in drug resistant gene silencing with nanoparticle-encapsulated siRNA to overcome MDR in human cancer.
