Strategies for tumor-directed delivery of siRNA.

INTRODUCTION: Current treatment of malignant tumors relies predominantly on chemotherapy delivering a single antineoplastic drug or a combination of two or more drugs intravenously. Problems with such treatments can include the killing of healthy cells, adverse side effects and chemoresistance. As cancer basically results from different types of mutation leading to the overexpression or suppression of the signaling cascades responsible for cancer cell survival and proliferation, tailor-made approaches capable of interfering precisely with those pathways are the potential revolutionary tools that could pave the way for highly effective cancer therapy. AREAS COVERED: This review summarizes recent progress in the identification and validation of the target genes for cancer gene therapy using small interfering RNA (siRNA) technology and, more importantly, the delivery strategies that have been designed and implemented for tumor-directed delivery of siRNAs. EXPERT OPINION: Cancer-targeted delivery of a gene in order to produce a particular protein (such as a tumor-suppressor or a nucleic acid sequence that can silence the expression of a specific gene, such as an oncogene or an antiapoptotic gene) is the most promising concept for cancer treatment in the future. siRNA has the ability to recognize and cleave a specific mRNA, thus inhibiting the expression of a particular protein. The success of targeted gene silencing as a potential cancer therapeutic demands the development of more effective delivery devices and the removal of siRNA off-target effects.