[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
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