PMID- 11943407
OWN - NLM
STAT- MEDLINE
DCOM- 20020702
LR  - 20220410
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 80
IP  - 1-3
DP  - 2002 Apr 23
TI  - Efficient intracellular drug and gene delivery using folate receptor-targeted 
      pH-sensitive liposomes composed of cationic/anionic lipid combinations.
PG  - 309-19
AB  - pH-sensitive liposomes are designed to promote efficient release of entrapped 
      agents in response to low pH. In this study, novel pH-sensitive liposomes 
      consisting of cationic/anionic lipid combinations are evaluated for intracellular 
      drug and gene delivery. First, liposomes composed of egg phosphatidylcholine, 
      dimethyldioctadecylammonium bromide (DDAB), cholesteryl hemisuccinate (CHEMS), 
      and Tween-80 (25:25:49:1, mol/mol) were shown to stably entrap calcein at pH 7.4 
      and undergo rapid content release and irreversible aggregation under acidic pH. 
      Compared to pH-sensitive liposomes incorporating 
      dioleoylphosphatidylethanolamine, these liposomes showed improved retention of 
      pH-sensitivity in the presence of serum. The folate receptor (FR), which is 
      amplified in a wide variety of human tumors, could be targeted by incorporating 
      0.1 mol% folate-polyethyleneglycol-phosphatidylethanolamine (f-PEG-PE) into 
      liposomes. f-PEG-PE has been shown to facilitate FR-mediated endocytosis of 
      liposomes into KB human oral cancer cells, which express amplified FR. 
      FR-targeted pH-sensitive liposomes produced increased cytosolic release of 
      entrapped calcein, as shown by fluorescence microscopy, and enhanced cytotoxicity 
      of entrapped cytosine-beta-D-arabinofuranoside, as shown by an 11-fold reduction 
      in the IC(50) in KB cells, compared to FR-targeted non-pH-sensitive liposomes. 
      Furthermore, FR-targeted pH-sensitive liposomes composed of DDAB/CHEMS/f-PEG-PE, 
      combined with polylysine-condensed plasmid DNA, were shown to mediate FR-specific 
      delivery of a luciferase reporter gene into KB cells in the presence of 10% 
      serum. These findings suggest that cationic lipid-containing pH-sensitive 
      liposomes, combined with FR targeting, are effective vehicles for intracellular 
      drug and gene delivery.
FAU - Shi, Guangfeng
AU  - Shi G
AD  - Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The 
      Ohio State University, Rm 542 LM Parks Hall, 500 W. 12th Ave., Columbus, OH 
      43210, USA.
FAU - Guo, Wenjin
AU  - Guo W
FAU - Stephenson, Stacy M
AU  - Stephenson SM
FAU - Lee, Robert J
AU  - Lee RJ
LA  - eng
GR  - R01 CA79758-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Anions)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cations)
RN  - 0 (Folate Receptors, GPI-Anchored)
RN  - 0 (Lipids)
RN  - 0 (Liposomes)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Anions/administration & dosage/pharmacokinetics
MH  - *Carrier Proteins/metabolism
MH  - Cations/administration & dosage/pharmacokinetics
MH  - Chemistry, Pharmaceutical
MH  - Drug Delivery Systems/*methods
MH  - Folate Receptors, GPI-Anchored
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Intracellular Fluid/*drug effects/metabolism
MH  - Lipids/*administration & dosage/pharmacokinetics
MH  - Liposomes/*administration & dosage/pharmacokinetics
MH  - *Receptors, Cell Surface
EDAT- 2002/04/12 10:00
MHDA- 2002/07/03 10:01
CRDT- 2002/04/12 10:00
PHST- 2002/04/12 10:00 [pubmed]
PHST- 2002/07/03 10:01 [medline]
PHST- 2002/04/12 10:00 [entrez]
AID - S0168365902000172 [pii]
AID - 10.1016/s0168-3659(02)00017-2 [doi]
PST - ppublish
SO  - J Control Release. 2002 Apr 23;80(1-3):309-19. doi: 
      10.1016/s0168-3659(02)00017-2.