Metal Chelation Modulates Phototherapeutic Properties of Mitoxantrone-Loaded Porphyrin-Phospholipid Liposomes

Mol Pharm. 2016 Feb 1;13(2):420-7. doi: 10.1021/acs.molpharmaceut.5b00653. Epub 2015 Dec 31.


Liposomes incorporating porphyrin-phospholipid (PoP) can be formulated to release entrapped contents in response to near-infrared (NIR) laser irradiation. Here, we examine effects of chelating copper or zinc into the PoP. Cu(II) and Zn(II) PoP liposomes, containing 10 molar % HPPH-lipid, exhibited unique photophysical properties and released entrapped cargo in response to NIR light. Cu-PoP liposomes exhibited minimal fluorescence and reduced production of reactive oxygen species upon irradiation. Zn-PoP liposomes retained fluorescence and singlet oxygen generation properties; however, they rapidly self-bleached under laser irradiation. Compared to the free base form, both Cu- and Zn-PoP liposomes exhibited reduced phototoxicity in mice. When loaded with mitoxantrone and administered intravenously at 5 mg/kg to mice bearing human pancreatic cancer xenografts, synergistic effects between the drug and the light treatment (for this particular dose and formulation) were realized with metallo-PoP liposomes. The drug-light-interval affected chemophototherapy efficacy and safety.

Keywords: Chemophototherapy; light-triggered; liposomes; metalloporphyrins; mitoxantrone; photobleaching; porphyrin-phospholipid; tumor ablation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Copper / chemistry
  • Humans
  • Infrared Rays
  • Lasers
  • Liposomes / chemistry*
  • Male
  • Mice
  • Mice, Nude
  • Mitoxantrone / chemistry
  • Mitoxantrone / pharmacology*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Phospholipids / chemistry*
  • Phototherapy*
  • Porphyrins / chemistry*
  • Singlet Oxygen / chemistry
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • Zinc / chemistry*


  • Liposomes
  • Phospholipids
  • Porphyrins
  • Singlet Oxygen
  • Copper
  • Mitoxantrone
  • Zinc