Small interfering RNA for cancer treatment: overcoming hurdles in delivery

Abstract

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

Keywords: 1,3-propanediol, PEG-b-PDMAEMA-b-Ppy; 2-propylacrylicacid, PAH-b-PDMAPMA-b-PAH; APOB, apolipoprotein B; AQP-5, aquaporin-5; AZEMA, azidoethyl methacrylate; Atufect01, β-l-arginyl-2,3-l-diaminopropionicacid-N-palmityl-N-oleyl-amide trihydrochloride; AuNPs, gold nanoparticles; B-PEI, branched polyethlenimine; BMA, butyl methacrylate; CFTR, cystic fibrosis transmembrane conductance regulator gene; CHEMS, cholesteryl hemisuccinate; CHOL, cholesterol; CMC, critical micelles concentration; Cancer; DC-Chol, 3β-[N-(N′,N′-dimethylaminoethane)carbamoyl]cholesterol; DMAEMA, 2-dimethylaminoethyl methacrylate; DNA, deoxyribonucleic acid; DOPC, dioleylphosphatidyl choline; DOPE, dioleylphosphatidyl ethanolamine; DOTAP, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate; DOTMA, N-[1-(2,3-dioleyloxy)propy]-N,N,N-trimethylammoniumchloride; DOX, doxorubicin; DSGLA, N,N-dis-tearyl-N-methyl-N-2[N′-(N2-guanidino-l-lysinyl)] aminoethylammonium chloride; DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholine; DSPE, 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine; DSPE-MPEG, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (ammonium salt); DSPE-PEG-Mal: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (mmmonium salt), EPR; Liposomes; Micelles; N-acetylgalactosamine, HIF-1α; Nanomedicine; PE-PCL-b-PNVCL, pentaerythritol polycaprolactone-block-poly(N-vinylcaprolactam); PLA, poly-l-arginine; PLGA, poly lactic-co-glycolic acid; PLK-1, polo-like kinase 1; PLL, poly-l-lysine; PPES-b-PEO-b-PPES, poly(4-(phenylethynyl)styrene)-block-PEO-block-poly(4-(phenylethynyl)styrene); PTX, paclitaxel; PiRNA, piwi-interacting RNA; Polymer; RES, reticuloendothelial system; RGD, Arg-Gly-Asp peptide; RISC, RNA-induced silencing complex; RNA, ribonucleic acid; RNAi, RNA interference; RNAse III, ribonuclease III enzyme; SEM, scanning electron microscope; SNALP, stable nucleic acid-lipid particles; SiRNA, short interfering rNA; Small interfering RNA (siRNA); S–Au, thio‒gold; TCC, transitional cell carcinoma; TEM, transmission electron microscopy; Tf, transferrin; Trka, tropomyosin receptor kinase A; USPIO, ultra-small superparamagnetic iron oxide nanoparticles; UV, ultraviolet; VEGF, vascular endothelial growth factor; ZEBOV, Zaire ebola virus; enhanced permeability and retention, Galnac; hypoxia-inducible factor-1α, KSP; kinesin spindle protein, LDI; lipid-protamine-DNA/hyaluronic acid, MDR; lysine ethyl ester diisocyanate, LPD/LPH; messenger RNA, MTX; methotrexate, NIR; methoxy polyethylene glycol-polycaprolactone, mRNA; methoxypoly(ethylene glycol), MPEG-PCL; micro RNA, MPEG; multiple drug resistance, MiRNA; nanoparticle, NRP-1; near-infrared, NP; neuropilin-1, PAA; poly(N,N-dimethylacrylamide), PDO; poly(N-isopropyl acrylamide), pentaerythritol polycaprolactone-block-poly(N-isopropylacrylamide); poly(acrylhydrazine)-block-poly(3-dimethylaminopropyl methacrylamide)-block-poly(acrylhydrazine), PCL; poly(ethylene glycol)-block-poly(2-dimethylaminoethyl methacrylate)-block poly(pyrenylmethyl methacrylate), PEG-b-PLL; poly(ethylene glycol)-block-poly(l-lysine), PEI; poly(ethylene oxide)-block-poly(2-(diethylamino)ethyl methacrylate)-stat-poly(methoxyethyl methacrylate), PEO-b-PCL; poly(ethylene oxide)-block-poly(Ε-caprolactone), PE-PCL-b-PNIPAM; poly(Ε-caprolactone), PCL-PEG; poly(Ε-caprolactone)-polyethyleneglycol-poly(l-histidine), PCL-PEI; polycaprolactone-polyethyleneglycol, PCL-PEG-PHIS; polycaprolactone-polyethylenimine, PDMA; polyethylenimine, PEO-b-P(DEA-Stat-MEMA.

Graphical abstract

Figure 1

Steps in RISC formation and function. Reprinted with the permission from Ref. . Copyright © 2012, ACS Publications.

Figure 2

Schematic representation of the elaboration of the transferrin targeted pDNA- or siRNA-CDP nanoparticles (RONDEL). Reprinted with the permission from Ref. . Copyright © 2011, Royal Society of Chemistry.

Figure 3

The formation process of liposome/phosphate/calcium (LPC) nanoparticles. Reprinted with the permission from Ref. . Copyright © 2010, Taylor & Francis Group.

Figure 4

Models of different polymeric micellar structures for siRNA delivery. (A) Polymer-siRNA conjugates complexed with polycation. (B) Block copolymers complexed with siRNA. Reprinted with the permission from Ref. . Copyright © 2012, Elsevier.