Cationic copolymers nanoparticles for nonviral gene vectors: synthesis, characterization, and application in gene delivery.
The major aim of nonviral delivery systems for gene therapy is to mediate high levels of gene expression with low toxicity. Nowadays, one of the most successful synthetic polycations used in gene delivery research is poly(ethylenimine) (PEI) in its high-molecular weight (HMW) branched form. However, PEI is not the ideal transfection agent in vivo because of its overwhelming cytotoxicity. To overcome its toxic effects with a minimal impact on transfection efficiency, PEI has been conjugated with several nonionic biocompatible polymers. Here, we describe the synthesis of nanosized particles consisting of HMW PEI (25 kDa) crosslinked with poly(epsilon-caprolactone) (PCL, 50-60 kDa), a biodegradable aliphatic polyester. PCL was modified by the insertion of glycidyl groups able to condense with the amines of PEI to chemically bind PEI onto PCL. The nanoparticles obtained have been characterized in relation to their physicochemical and biological properties, and the results are extremely promising in terms of low cell toxicity and high transfection efficiency. These biological effects might be related to the peculiar DNA binding to covalently connected polymeric nanoparticles, without the formation of entangled DNA/polymer-soluble aggregates.
d'Ayala
Giovanna Gomez
GG
Institute of Polymers Chemistry and Technology, CNR, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy.
Calarco
Anna
A
Malinconico
Mario
M
Laurienzo
Paola
P
Petillo
Orsolina
O
Torpedine
Angela
A
Peluso
Gianfranco
G
D002152:Calorimetry, Differential Scanning; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008422:Materials Testing; D015394:Molecular Structure; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry; D013718:Tensile Strength; D014162:Transfection
D002412:Cations; D011091:Polyesters; C016240:polycaprolactone; D011094:Polyethyleneimine; D004247:DNA