Rapid Light-Triggered Drug Release in Liposomes Containing Small Amounts of Unsaturated and Porphyrin-Phospholipids

Small. 2016 Jun;12(22):3039-47. doi: 10.1002/smll.201503966. Epub 2016 Apr 28.


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.

Keywords: PoP liposomes; chemophototherapy; chemotherapy; light-triggered release; porphyrin-phospholipid.

MeSH terms

  • Animals
  • Doxorubicin / chemistry
  • Drug Liberation / radiation effects
  • Humans
  • Light*
  • Liposomes / chemistry*
  • Mice
  • Phospholipids / chemistry*
  • Porphyrins / chemistry*


  • Liposomes
  • Phospholipids
  • Porphyrins
  • Doxorubicin