Blood Interactions, Pharmacokinetics, and Depth-Dependent Ablation of Rat Mammary Tumors with Photoactivatable, Liposomal Doxorubicin

Mol Cancer Ther. 2019 Mar;18(3):592-601. doi: 10.1158/1535-7163.MCT-18-0549. Epub 2018 Dec 26.


Photosensitizers can be integrated with drug delivery vehicles to develop chemophototherapy agents with antitumor synergy between chemo- and photocomponents. Long-circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes. Hematological effects of endotoxin-minimized LC-Dox-PoP were characterized via standardized assays. In vitro interaction with erythrocytes, platelets, and plasma coagulation cascade were generally unremarkable, whereas complement activation was found to be similar to that of commercial Doxil. Blood partitioning suggested that both the Dox and PoP components of LC-Dox-PoP were stably entrapped or incorporated in liposomes. This was further confirmed with pharmacokinetic studies in Fischer rats, which showed the PoP and Dox components of the liposomes both had nearly identical, long circulation half-lives (25-26 hours). In a large orthotopic mammary tumor model in Fischer rats, following intravenous dosing (2 mg/kg Dox), the depth of enhanced Dox delivery in response to 665 nm laser irradiation was over 1 cm. LC-Dox-PoP with laser treatment cured or potently suppressed tumor growth, with greater efficacy observed in tumors 0.8 to 1.2 cm, compared with larger ones. The skin at the treatment site healed within approximately 30 days. Taken together, these data provide insight into nanocharacterization and photo-ablation parameters for a chemophototherapy agent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy
  • Cell Line, Tumor
  • Disease Models, Animal
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Delivery Systems*
  • Female
  • Humans
  • Mammary Neoplasms, Animal / chemistry
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / pathology
  • Phospholipids / chemistry
  • Phospholipids / pharmacology*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology
  • Rats
  • Rats, Inbred F344


  • Phospholipids
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin