PMID- 7918553
OWN - NLM
STAT- MEDLINE
DCOM- 19941121
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1195
IP  - 1
DP  - 1994 Oct 12
TI  - Oligonucleotide-cationic liposome interactions. A physicochemical study.
PG  - 115-23
AB  - Cationic liposomes are effective in delivering antisense oligonucleotides into 
      cells in culture, but their interactions with the oligonucleotides are poorly 
      understood. We studied the aggregation and fusion reactions during the formation 
      of cationic lipid/oligonucleotide complexes in solution and their interactions 
      with lipid bilayers. Phosphorothioate oligonucleotides (15-mer) were complexed 
      with cationic liposomes composed of dimethyldioctadecylammonium bromide (DDAB) 
      and dioleoylphosphatidylethanolamine (DOPE) at 8:15 molar ratio or of a 
      commercial formulation DOTAP 
      (N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammoniummethylsul fate), at 
      different ratios with apparent -/+ charge ratios of 0.03-5.6. Mean size of the 
      complexes increased with -/+ ratio so that at charge ratios 0.4-2.0 the size 
      increased by at least an order magnitude due to the oligonucleotide induced 
      aggregation. Resonance energy transfer experiments showed that in addition to 
      aggregation oligonucleotides induced fusion of cationic liposomes, but the fusion 
      was rate-controlled by the initial aggregation step. Rate constants for 
      oligonucleotide induced aggregation were dependent on lipid concentration and 
      were in the range of (0.2-1).10(7) M-1 s-1 and (1-10).10(7) M-1 s-1 for DDAB/DOPE 
      and DOTAP, respectively. Increase in oligonucleotide concentration induced the 
      aggregation and fusion until at high -/+ ratios electrostatic repulsion of 
      negative surfaces inhibited further aggregation and fusion. DOTAP/oligonucleotide 
      complexes did not induce leakage of calcein from neutral EPC liposomes, but did 
      cause leakage at -/+ charge ratios of < 0.7 and > 2.0 from EPC/DOPE liposomes. 
      Also at -/+ charge ratios below 0.8 DOTAP/oligonucleotide complexes induced 
      leaking from negatively charged DPPC/DPPG liposomes. These results indicate that 
      either phosphatidylethanolamine or negative charge are required in the cell 
      membrane for fusion of cationic liposome-oligonucleotide complexes. The ratio of 
      oligonucleotide to cationic lipid is critical in determining the physicochemical 
      properties of the mixture.
FAU - Jaaskelainen, I
AU  - Jaaskelainen I
AD  - Department of Pharmaceutical Technology, University of Kuopio, Finland.
FAU - Monkkonen, J
AU  - Monkkonen J
FAU - Urtti, A
AU  - Urtti A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Cations)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Liposomes)
RN  - 0 (Oligonucleotides)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Phosphatidylethanolamines)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 13146-86-6 (didodecyldimethylammonium)
RN  - 76391-83-8 (1,2-dielaidoylphosphatidylethanolamine)
RN  - MR86K0XRQP (1,2-dioleoyloxy-3-(trimethylammonium)propane)
SB  - IM
MH  - Cations/chemistry
MH  - Energy Transfer
MH  - Fatty Acids, Monounsaturated
MH  - Liposomes/*chemistry
MH  - Oligonucleotides/*chemistry
MH  - Oligonucleotides, Antisense/chemistry
MH  - Phosphatidylethanolamines
MH  - Quaternary Ammonium Compounds
EDAT- 1994/10/12 00:00
MHDA- 1994/10/12 00:01
CRDT- 1994/10/12 00:00
PHST- 1994/10/12 00:00 [pubmed]
PHST- 1994/10/12 00:01 [medline]
PHST- 1994/10/12 00:00 [entrez]
AID - 0005-2736(94)90017-5 [pii]
AID - 10.1016/0005-2736(94)90017-5 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1994 Oct 12;1195(1):115-23. doi: 
      10.1016/0005-2736(94)90017-5.