Lipid-coated nano-calcium-phosphate (LNCP) for gene delivery.
While calcium-phosphate has been used to deliver plasmid DNA (pDNA) for decades, the method is typically characterized by low and irreproducible transfection efficiency relative to the other non-viral approaches, such as liposomes and polymers. Here we report a novel gene transfer vector comprising lipid-coated nano-calcium-phosphate (LNCP) that provides consistently efficient and satisfactory pDNA delivery. It is based on core-shell nanoparticles comprising a calcium-phosphate core and a cationic lipid shell. This method, in contrast to the solution precipitation methods used in the past, yields colloidally stable calcium-phosphate nanoparticles inside the cationic liposomes. Our results indicate that the particle size and the size distribution of the LNCP remain virtually unchanged even after 21 days of storage. Atomic force microscopy measurements reveal that the LNCP have a 5-fold higher rigidity than common cationic liposomes. The LNCP transfected pDNA 24 times greater than the naked pDNA and 10-fold greater relative to the standard calcium-phosphate precipitation preparations, suggesting that the LNCP may have potential as a novel transfection agent for gene therapy.
Zhou
Chenguang
C
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Yu
Bo
B
Yang
Xiaojuan
X
Huo
Tianyao
T
Lee
L James
LJ
Barth
Rolf F
RF
Lee
Robert J
RJ
D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D002412:Cations; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013054:Spectrophotometry, Atomic; D014162:Transfection
D002130:Calcium Phosphates; D002412:Cations; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D004247:DNA; C020243:calcium phosphate