Gene delivery with bisphosphonate-stabilized calcium phosphate nanoparticles.
Nucleic acid drugs are promising new therapeutics, due to their possible applications in a wide variety of diseases and their strong targeting potential and associated lower off-target effects compared to conventional pharmaceuticals. However, their poor intracellular bioavailability and rapid degradation hinder their development as drugs. Therefore, efficient delivery is a major challenge. Various systems have been developed to overcome this problem. The entrapment of genetic material into nanoparticles constitutes a promising approach to increase the in vitro and in vivo transfection activity. Calcium phosphate-DNA co-precipitates have been used for gene delivery for more than 35 years and have the advantage of being nontoxic, easy to produce, and having the ability to complex nucleic acids leading to efficient transfection. Conventional synthetic methods yield particles that are only stable for a short period of time. Herein is proposed a versatile, surfactant-free method to stabilize calcium phosphate-DNA nanoparticles based on the use of poly(ethylene glycol)-functionalized bisphosphonate. The strength of the interaction between the bisphosphonate and the calcium phosphate enabled the formation of stable, but bioresorbable particles of around 200 nm, which exhibited physical stability over several days. Additionally, the nanoparticles revealed good and sustained ability to transfect cells while displaying low toxicity.
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland.
Elisabeth V
EV
Giger
Josep
J
Puigmartí-Luis
Rahel
R
Schlatter
Bastien
B
Castagner
Petra S
PS
Dittrich
Jean-Christophe
JC
Leroux
D002130:Calcium Phosphates / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage*; D004164:Diphosphonates / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D014162:Transfection
D002130:Calcium Phosphates; D004164:Diphosphonates; D011092:Polyethylene Glycols; D004247:DNA; C020243:calcium phosphate