Rapid Light-Triggered Drug Release in Liposomes Containing Small Amounts of Unsaturated and Porphyrin-Phospholipids.
Prompt membrane permeabilization is a requisite for liposomes designed for local stimuli-induced intravascular release of therapeutic payloads. Incorporation of a small amount (i.e., 5 molar percent) of an unsaturated phospholipid, such as dioleoylphosphatidylcholine (DOPC), accelerates near infrared (NIR) light-triggered doxorubicin release in porphyrin-phospholipid (PoP) liposomes by an order of magnitude. In physiological conditions in vitro, the loaded drug can be released in a minute under NIR irradiation, while liposomes maintain serum stability otherwise. This enables rapid laser-induced drug release using remarkably low amounts of PoP (i.e., 0.3 molar percent). Light-triggered drug release occurs concomitantly with DOPC and cholesterol oxidation, as detected by mass spectrometry. In the presence of an oxygen scavenger or an antioxidant, light-triggered drug release is inhibited, suggesting that the mechanism is related to singlet oxygen mediated oxidization of unsaturated lipids. Despite the irreversible modification of lipid composition, DOPC-containing PoP liposome permeabilization is transient. Human pancreatic xenograft growth in mice is significantly delayed with a single chemophototherapy treatment following intravenous administration of 6 mg kg(-1) doxorubicin, loaded in liposomes containing small amounts of DOPC and PoP.
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Dandan
D
Luo
Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Nasi
N
Li
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Kevin A
KA
Carter
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Cuiyan
C
Lin
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Jumin
J
Geng
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Shuai
S
Shao
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Wei-Chiao
WC
Huang
Department of Physics, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Yueling
Y
Qin
Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
G Ekin
GE
Atilla-Gokcumen
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Jonathan F
JF
Lovell
D000818:Animals; D004317:Doxorubicin / Q000737:chemistry; D065546:Drug Liberation / Q000528:radiation effects; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D010743:Phospholipids / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*
D008081:Liposomes; D010743:Phospholipids; D011166:Porphyrins; D004317:Doxorubicin
PoP liposomes; chemophototherapy; chemotherapy; light-triggered release; porphyrin-phospholipid