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Rapid Light‐Triggered Drug Release in Liposomes Containing Small Amounts of Unsaturated and Porphyrin–Phospholipids
Author(s) -
Luo Dandan,
Li Nasi,
Carter Kevin A.,
Lin Cuiyan,
Geng Jumin,
Shao Shuai,
Huang WeiChiao,
Qin Yueling,
AtillaGokcumen G. Ekin,
Lovell Jonathan F.
Publication year - 2016
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201503966
Subject(s) - liposome , phospholipid , chemistry , porphyrin , biophysics , singlet oxygen , drug carrier , doxorubicin , drug delivery , chromatography , membrane , biochemistry , oxygen , organic chemistry , chemotherapy , medicine , surgery , biology
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.