Figure 5.

Junction opener 1 increases tumor penetration and efficacy of PEGylated liposomal doxorubicin (PLD)/Doxil™. Studies were performed in mice with mammary fat pad tumors derived from ovc316 cells (135, 206). Ovc316 cells are Her2/neu positive epithelial tumor cells derived from an ovarian cancer biopsy. (A) Scheme of experiment on tumor penetration of PLD. Mice were intravenously injected with PBS or JO-1 (2 mg/kg) followed by PLD or PBS 1 h later. Two hours after PBS or PLD injection, mice were sacrificed and tumors harvested. (B) Immunofluorescence analysis for PLD on tumor sections with anti-PEG antibodies. PLT appears in red. The scale bar is 20 μm. Notably, free PEG is poorly detected by ELISA or immunohistochemistry (184). (C) PLD concentrations in tumors measured by ELISA (N = 3). (D) Therapy study in mice with ovc316 tumors. Treatment was started when tumors reached a volume of 100 mm³ (D0). Mice were injected intravenously with 2 mg/kg JO-1 or PBS, followed by an intravenous injection of PLD (1 mg/kg) or PBS 1 h later. Treatment was repeated weekly (N = 5).