Porphyrin-phospholipid liposomes and chemophototherapy.

We have developed liposomes that are doped with a small amount of a photosensitizing lipid; porphyrin-phospholipid (PoP).^[1] Long-circulating doxorubicin (Dox) in porphyrin–phospholipid (PoP) liposomes (LC-Dox-PoP) is similar to the FDA-approved liposomal doxorubicin form of Doxil, but incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes.^[2] A liposomal irinotecan formulation has been made in a similar manner based on the FDA-approved liposomal Onivyde.^[3] Drugs loaded in PoP liposomes, as well as the PoP itself are stable and exhibit long circulation times in blood. However, red laser irradiation rapidly releases the entrapped drug from the carrier. When mouse or rat tumors are treated with these chemophototherapy agents, a single treatment is frequently sufficient to ablate established tumors at a relatively low chemotherapy dose of drug. Pharmacokinetic analysis shows that a major mechanism for the efficacy pertains to enhanced drug delivery following permeabilization of tumor blood vessels damaged by PDT. We will discuss our experience and outlook for this approach to chemophotherapy as a strong ablation modality with systemic drug delivery. [ABSTRACT FROM AUTHOR]