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 (kΔ) for liposome suspensions in H2O and in D2O solvents, as well as the absolute and the apparent 1O2 production quantum yields (ΦΔ). Despite the characteristic differences in their photophysical behavior, namely in ΦΔ 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.