A review of the current status of siRNA nanomedicines in the treatment of cancer

Abstract

RNA interference currently offers new opportunities for gene therapy by the specific extinction of targeted gene(s) in cancer diseases. However, the main challenge for nucleic acid delivery still remains its efficacy through intravenous administration. Over the last decade, many delivery systems have been developed and optimized to encapsulate siRNA and to specifically promote their delivery into tumor cells and improve their pharmacokinetics for anti-cancer purposes. This review aims to sum up the potential targets in numerous pathways and the properties of recently optimized siRNA synthetic nanomedicines with their preclinical applications and efficacy. Future perspectives in cancer treatment are discussed including promising concomitant treatment with chemotherapies or other siRNA. The outcomes in human clinical trials are also presented.

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

“…Here, we report on novel cationic phosphorus containing dendrimers of 3rd and 4th generations grafted with piperidine groups on the periphery that were synthesized and tested as siRNA carriers for RNAi-based cancer gene therapy with a chemotherapeutic combination approach. The objectives of this original study can be listed as follows: (1) to synthesize new piperidine-terminated cationic phosphorus dendrimers; (2) to evaluate the formation of complexes between dendrimers and siRNAs and their stability; (3) to assess the delivery potential of dendrimers by analyzing cellular uptake of dendriplexes; and (4) to determine the ability of dendriplexes to inhibit cancer cell growth, including their combination with the common chemotherapeutic agent 5-fluorouracil (5-FU).…”

“…The possibility to knock-down a gene-specific therapeutic activity in the treatment of cancers has been intensively documented [2]. However, using siRNAs as anticancer agents requires intravenous administration associated with several intrinsic problems, such as their degradation by plasma nucleases, poor ability to penetrate into cells and rapid systemic removal by glomerular filtration.…”

“…However, using siRNAs as anticancer agents requires intravenous administration associated with several intrinsic problems, such as their degradation by plasma nucleases, poor ability to penetrate into cells and rapid systemic removal by glomerular filtration. Moreover, intracellular breakdown by lysosomal enzymes diminishes the activity of siRNA therapeutics [2,3]. Thus, overcoming the barriers to siRNA delivery remains one of the main issues in the development of RNAi strategy to combat cancers [2].…”

“…Moreover, intracellular breakdown by lysosomal enzymes diminishes the activity of siRNA therapeutics [2,3]. Thus, overcoming the barriers to siRNA delivery remains one of the main issues in the development of RNAi strategy to combat cancers [2].…”

pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery

“…When the tumors grew to approximately 70 mm 3 , the mice were given intravenous (iv) injections of CMCS-SiSf-CL at a dose of 1.0 mg/kg Cy5-siRNA (20 nM) or free Cy5-siRNA. After 6 hours of injection, the in vivo images were observed with the in vivo real-time fluorescence imaging system (IVIS) Spectrum (Cailper PerkinElemer, Waltham, MA, USA) at appropriate wavelength (Cy5: excitation wavelength of 640 nm, emission wavelength of 680 nm).…”