Types of nanoparticle systems used in siRNA delivery.

List of siRNA-based drugs targeting different diseases were in clinical trials.

siRNA and RNAi pricelist from Gene Link

Schematic diagram showing the preparation of (A) the multifunctional NP-PEI-siRNA-CTX nanovector and (B) intracellular uptake, extracellular trafficking, and processing of the nanovector in tumor cells. Reproduced with permission from ref. [].

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195. Lee SH, Choi SH, Kim SH, Park TG. Thermally sensitive cationic polymer nanocapsules for specific cytosolic delivery and efficient gene silencing of siRNA: Swelling induced physical disruption of endosome by cold shock. 2008;125:25-32

194. Kim C, Lee Y, Lee SH, Kim JS, Jeong JH, Park TG. Self-Crosslinked Polyethylenimine Nanogels for Enhanced Intracellular Delivery of siRNA. 2011;19:166-171

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183. Blackburn WH, Dickerson EB, Smith MH, McDonald JF, Lyon LA. Peptide-Functionalized Nanogels for Targeted siRNA Delivery. 2009;20:960-968

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182. Raemdonck K, Van Thienen TG, Vandenbroucke RE, Sanders NN, Demeester J, De Smedt SC. Dextran microgels for time-controlled delivery of siRNA. 2008;18:993-1001

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Ross . developed brain cancer-targeted multifunctional polymeric nanoparticles consisting of tumor vascular targeting F3 peptides, photosensitizers for photodynamic therapy (PDT), and iron oxide for MRI []. The targeted delivery of photodynamic agents to tumor sites via nanoparticles is one approach to overcoming the disadvantages of prolonged cutaneous photosensitization during PDT. To conjugate targeting peptides onto the nanoparticles specifically, first, amine-functionalized, photofrin and iron oxide-encapsulated polyacrylamide nanoparticles were preparede nanoparticles apsulated consisting of a surface-localized rgeting. , and the water-soluble sulfo-SMCC was added to couple with surface amines on nanoparticles. The reaction mixture was further treated with succinimidyl succinate ester of PEG2000. And the thiol groups of F3 peptides, pretreated with Traut's reagent, were lastly conjugated to the maleimide-functionalized nanoparticles. The targeted nanoparticles performed well during PDT and significantly improved survival rate in a glioma-bearing orthotopic rat model. SMCC may be replaced by heterobifunctional PEG molecules (NHS-PEG-MAL) to functionalize amine-modified nanoparticles. Zhang . used NHS-(PEG)2-MAL and NHS-(PEG)12-MAL to introduce maleimide functionalities onto the magnetic nanoparticles []. A thiol-modified siRNA and CTX were attached to the amine-functionalized pH-sensitive PEI-coated iron oxide nanoparticles via NHS-(PEG)2-MAL and NHS-(PEG)12-MAL, respectively (Figure A). The dodecaethyleneglycol linker for CTX facilitated targeted ligand delivery by providing a more flexible linker, thereby enhancing the peptide's ability to bind to a target receptor. pH-sensitive surface coating layers improved the presentation and availability of cationic CTX on the nanovector surfaces by introducing electrostatic charge repulsion between CTX and surface moieties (Figure B).

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173. Wang XM, Yu B, Ren W, Mo XK, Zhou CG, He HY. . Enhanced hepatic delivery of siRNA and microRNA using oleic acid based lipid nanoparticle formulations. 2013;172:690-698

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172. Carmona S, Jorgensen MR, Kolli S, Crowther C, Salazar FH, Marion PL. . Controlling HBV replication in vivo by intravenous administration of triggered PEGylated siRNA-nanoparticles. 2009;6:706-717