Chemophototherapy Overcomes Doxorubicin Resistance in Human Ovarian Cancer Cells

Abstract

Porphyrin-phospholipid (PoP) liposomes loaded with Doxorubicin have been demonstrated to be an efficient vehicle for chemophototherapy (CPT). Multi-drug resistance (MDR) of cancer cells is a known resistance mechanism for cancer chemotherapies. We report a phototherapeutic measure to overcome Dox-resistance using Doxorubicin (Dox)-loaded PoP liposomes. In vitro studies using free Dox or Dox loaded into liposomes with 2 mol.% showed human ovarian carcinoma A2780 cells were more susceptible to these drugs compared to the corresponding Dox-resistant A2780-R cells. In contrast, when CPT was applied with LC-Dox-PoP liposomes, effective killing of both non-resistant and resistant A2780 cell lines was observed. An in vivo study to assess the efficiency of LC-Dox-PoP liposomes with phototreatment showed effective tumor shrinkage and prolonged survival of athymic nude mice bearing A2780-R tumor xenografts. Biodistribution analysis demonstrated enhanced tumoral drug uptake in Dox-resistant tumors with CPT, pointing to the likelihood that increased drug delivery overcame resistance mechanisms to provide for improved anti-cancer therapy.