Singlet oxygen partition between the outer-, inner- And membrane-phases of photo/chemotherapeutic liposomes

Liposomes carrying membrane-embedded porphyrin-phospholipid (PoP) are capable of chemo- and photo-therapeutic modes of action, which make them a potential candidate material for next-generation cancer treatments. This study examines singlet oxygen (¹O₂) production and release by PoP liposomes carrying either no chemotherapeutic cargo (EMPTY), or those carrying either doxorubicin (DOX) or irinotecan (IRT) chemotherapy drugs. Herein, we developed a strategy to quantify the fraction of ¹O₂ lifetime spent in the three distinct local liposomal environments by obtaining four key pieces of information for each system: average ¹O₂ deactivation rate constants (k_Δ) for liposome suspensions in H₂O and in D₂O solvents, as well as the absolute and the apparent ¹O₂ production quantum yields (Φ_Δ). Despite the characteristic differences in their photophysical behavior, namely in Φ_Δ values, all three formulations of PoP liposomes were found to carry out ¹O₂ release in a similar manner. It was found that >80% of all sensitized ¹O₂ from the ensemble of PoP liposomes deactivates within the nanostructures themselves, with the largest portion (∼50%) deactivating in the lipid membrane specifically. Based on these findings, we conclude that the current design of the PoP liposomes is well suited for light-induced chemotherapeutic drug release. Importantly, the ¹O₂ partition quantification approach reported herein has potential to be a tool for characterizing nanoparticulate light-activated chemo- and phototherapeutic systems.