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Polymeric Nanoparticles as siRNA Drug Delivery System for Cancer Therapy: The Long Road to Therapeutic Efficiency
Frère, Antoine; Evrard, Brigitte; Mottet, Denis et al.
2016In Holban, Alina Maria; Grumezescu, Alexandru (Eds.) Nanoarchitectonics for Smart Delivery and Drug Targeting
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Keywords :
siRNA; Polymer; PEI; Polyplex; cancer; gene delivery; PEG; endosomal escape; proton sponge effect
Abstract :
[en] Polyplexes are nanoparticles composed of small-interfering RNA (siRNA) and natural or synthetic polymers. To meet the challenge of gene therapy and deliver siRNA into the cytoplasm of target cells, several barriers must be overcome. In this chapter, the main steps, from the formulation of polyplexes to the efficient release of the siRNA into the cytoplasm of cancer cells, are described, taking into account the different strategies used to overcome the obstacles linked to the formulation of this type of nanovector. To allow a parenteral administration of the nanocolloids, the polyplex production methods should result in identical, stable, and reproducible nanostructures. Charge interactions occur between the anionic siRNA and the cationic/amphiphilic polymer. Once in the blood circulation, polyplexes must keep their physical stability. The positively charged surface can cause aggregation of the nanoparticles with plasma proteins, as well as complement activation and recognition by the mononuclear phagocytic system, with a consequent reduction of their pharmacological activity. Polyethylene glycol (PEG) can be added on the surface of the nanovectors to confer “the stealth” properties and increase plasma half-life. Then, particles have to preferentially accumulate in the tumor tissue following an active or passive targeting. Endocytosis process enables the polyplex cellular uptake, but some strategies like “the proton sponge effect” have to be used to allow the escape of the nanovectors from the cellular endosomes. Once released into the cytoplasm, polymer and siRNA must dissociate for an effective degradation of the targeted mRNA, leading finally to a decrease of the corresponding protein.
Research center :
Centre Interfacultaire de Recherche du Médicament - CIRM
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Frère, Antoine ;  Université de Liège > Département de pharmacie > Pharmacie galénique
Evrard, Brigitte  ;  Université de Liège > Département de pharmacie > Pharmacie galénique
Mottet, Denis ;  Université de Liège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Piel, Géraldine ;  Université de Liège > Département de pharmacie > Pharmacie galénique
Language :
English
Title :
Polymeric Nanoparticles as siRNA Drug Delivery System for Cancer Therapy: The Long Road to Therapeutic Efficiency
Publication date :
25 July 2016
Main work title :
Nanoarchitectonics for Smart Delivery and Drug Targeting
Editor :
Holban, Alina Maria
Grumezescu, Alexandru
Publisher :
Elsevier
ISBN/EAN :
978-0-323-47347-7
Pages :
503-540
Peer reviewed :
Peer reviewed
Available on ORBi :
since 02 June 2016

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