Chemophototherapeutic Ablation of Doxorubicin‐Resistant Human Ovarian Tumor Cells^†

Abstract

Porphyrin‐phospholipid (PoP) liposomes loaded with Doxorubicin (Dox) have been demonstrated to be an efficient vehicle for chemophototherapy (CPT). Multidrug resistance (MDR) of cancer cells is a problematic phenomenon in which tumor cells develop resistance to chemotherapy. Herein, we report that Dox‐resistant tumor cells can be ablated using our previously described formulation termed long‐circulating Dox loaded in PoP liposomes (LC‐Dox‐PoP), which is a PEGylated formulation containing 2 mol. % of the PoP photosensitizer. In vitro studies using free Dox and LC‐Dox‐PoP showed that human ovarian carcinoma A2780 cells were more susceptible to Dox compared to the corresponding Dox‐resistant A2780‐R cells. When CPT was applied with LC‐Dox‐PoP liposomes, effective killing of both nonresistant and resistant A2780 cell lines was observed. An in vivo study to assess the efficiency of LC‐Dox‐PoP showed effective tumor shrinkage and prolonged survival of athymic nude mice bearing subcutaneous Dox‐resistant A2780‐R tumor xenografts when they were irradiated with a red laser. Biodistribution analysis demonstrated enhanced tumoral drug uptake in Dox‐resistant tumors with CPT, suggesting that increased drug delivery was sufficient to induce ablation of resistant tumor cells.